# US 2024/0199697 A1 · Compositions for Colon Cleansing and the Treatment of Gastrointestinal Disorders

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- Number: US 2024/0199697 A1
- Document ID: US20240199697A1
- Status: Published application
- Kind: A1
- Application number: 18/424,114
- Filed: 2024-01-26
- Published: 2024-06-20
- Earliest claimed: 2015-05-01
- Assignees: Ironwood Pharmaceuticals, Inc.
- Applicants: Ironwood Pharmaceuticals, Inc.
- Inventors: Mark G. Currie; Robert Solinga; Christopher Leitheiser
- Web page: https://patentgrep.com/patent/US20240199697A1

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 9/0031: {Rectum, anus}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/10: Laxatives
- A61P 35/00: Antineoplastic agents
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides peptides and compositions that are useful for the treatment of gastrointestinal disorders or for colon cleansing. The present invention also provides compositions and methods of treating gastrointestinal disorders and pharmaceutical compositions for accomplishing the same. In some embodiments, these pharmaceutical compositions include oral dosage forms.

## Claims

### Claim 1

A peptide or a pharmaceutically acceptable salt thereof, wherein the peptide comprises the amino acid sequence
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof; wherein
Xaa1 is BE or is absent;
Xaa2 is BK, Asn or is absent;
Xaa3 is Asn, Ser or is absent;
Xaa4 is Ser or is absent;
Xaa5 is Ser, Asn, Ile, BE or is absent;
Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), Hag, or Asp;
Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
Xaa9 is Glu, Asp, Ser, Thr, or Gln;
Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
Xaa11 is Cys, Ag, or penicillamine (Pen);
Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
Xaa13 is Asn or Leu;
Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
Xaa16 is Cys, Ag, Pen or Cth;
Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
Xaa19 is Cys, Ag or Pen;
Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
Xaa21 is absent or Asn;
wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro; and
wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16 and Xaa11 and Xaa19.

### Claim 2 (depends on 1)

The peptide or pharmaceutically acceptable salt thereof according to claim 1, wherein the N-terminus is capped with acetic acid, pentenoic acid, biotin, 4-Mepip, C12 alkyl carboxylic acid, C14 alkyl carboxylic acid, C16 alkyl carboxylic acid, or C18 alkyl carboxylic acid.

### Claim 3 (depends on 1, 2)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1 or 2, wherein the C-terminus is amidated.

### Claim 4 (depends on 1, 2, 3)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein
Xaa7 and Xaa12 are both Ag and a dicarba bond is present between Ag7 and Ag12;
Xaa7 and Xaa12 are both Cys and a disulfide bond is present between Cys7 and Cys12;
Xaa8 and Xaa16 are both Cys and a disulfide bond is present between Cys8 and Cys16;
Xaa7 is Cth and Xaa12 is Cys and a bond is present between Cth7 and Cys12;
Xaa8 is Cth and Xaa16 is Cys and a bond is present between Cth8 and Cys16;
Xaa11 and Xaa19 are Cys and a disulfide bond is present between Cys11 and Cys19; or
any combination thereof.

### Claim 5 (depends on 1, 2, 3)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein Xaa7 is allylglycine, Cth or Cys.

### Claim 6 (depends on 1, 2, 3)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein Xaa8 is Cys or cystathionine.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-6, wherein Xaa9 is Glu.

### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-7, wherein Xaa10 is Leu.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-8, wherein Xaa12 is Cys or allylglycine.

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-9, wherein Xaa14 is Val or Pro.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-10, wherein Xaa17 is Tyr or Thr.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-11, wherein Xaa20 is Tyr or is absent.

### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 1-12, wherein Xaa21 is absent.

### Claim 14 (depends on 1)

The peptide or pharmaceutically acceptable salt thereof according to claim 1, wherein:
Xaa1 is absent;
Xaa2 is absent;
Xaa3 is absent;
Xaa4 is absent;
Xaa5 is absent;
Xaa6 is absent;
Xaa7 is Ag, Cys, or Cth;
Xaa8 is Cys or Cth;
Xaa9 is Glu;
Xaa10 is Leu;
Xaa12 is Ag or Cys;
Xaa14 is Val or Pro;
Xaa17 is Tyr or Thr; and
Xaa20 is Tyr or is absent.

### Claim 15 (depends on 13)

The peptide or pharmaceutically acceptable salt thereof according to claim 13, wherein the peptide comprises the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 62)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
or
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH.

### Claim 16 (depends on 1)

The peptide or a pharmaceutically acceptable salt thereof according to claim 1, wherein the peptide comprises the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 3)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 4)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 5)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 6)
C14-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 7)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 8)
H-Cys Ag Glu Leu Cys Cys Asn Pro Ala Ag Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 9)
H-Asn Asp Asp Ag Glu Leu Cys Val Asn Val Ala Ag Thr Gly Cys Leu-
NH2;
(SEQ ID NO: 10)
H-Asn Asp Asp Cys Glu Leu Ag Val Asn Val Ala Cys Thr Gly Ag Leu-
NH2;
(SEQ ID NO: 11)
C18-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 12)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 13)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys-NH2;
(SEQ ID NO: 14)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 15)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 16)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 17)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 18)
H-Cys Cys Glu Leu Ag Cys Asn Pro Ala Cys Thr Gly Ag Tyr-NH2;
(SEQ ID NO: 19)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 20)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 21)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 22)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 23)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 24)
H-(4-F)Phe Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-
F)Phe-NH2;
(SEQ ID NO: 25)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 27)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 28)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys (4-F)Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 29)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu-NH2;
(SEQ ID NO: 30)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Cha-NH2;
(SEQ ID NO: 31)
H-Ag Cys Glu Cha Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 32)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys D-Tyr-NH2;
(SEQ ID NO: 33)
H-Ag Pen Glu Leu Cys Ag Asn Pro Ala Pen Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 34)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu Asn-NH2;
(SEQ ID NO: 35)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr Asn-NH2;
(SEQ ID NO: 36)
H-Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 37)
H-Ile Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-
NH2;
(SEQ ID NO: 38)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 39)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 40)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 41)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 42)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 44)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Cha Gly Cys Tyr-NH2;
(SEQ ID NO: 45)
H-Ag Cys Glu Leu Cys Ag Asn Leu Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 46)
H-Ag Cys Glu Leu Cys Ag Asn Sar Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 48)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 49)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 50)
H-Ag Cys Asp Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 51)
H-Ag Cys Ser Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 52)
H-Ag Cys Thr Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 53)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 54)
H-Ag Cys Gln Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 55)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 56)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 57)
H-Cys Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Ag-COOH;
(SEQ ID NO: 58)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 59)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 60)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 61)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 62)
H-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 63)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 65)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 66)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 67)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 72)
H-Cys Cys Glu Leu Cys Asn Val Ala Cth Tyr Gly Cys-COOH;
(SEQ ID NO: 73)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 74)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 75)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 76)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 77)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 78)
4-Mepip-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 79)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 80)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 81)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Phe Gly Cys-COOH;
(SEQ ID NO: 82)
H-Ag Ag Glu Leu Ag Ag Asn Pro Ala Ag Thr Gly Ag Tyr-COOH;
(SEQ ID NO: 83)
H-Cys Cth Glu Leu Cys Cys Asn Ala Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 84)
H-Asp Cys Glu Leu Cys Dpr Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 85)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Ser Gly Cys Tyr-NH2;
(SEQ ID NO: 86)
H-Cth Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 87)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 88)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 89)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 90)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 91)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
or
(SEQ ID NO: 92)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys-COOH.

### Claim 17

A peptide or a pharmaceutically acceptable salt thereof, wherein the peptide consists of the amino acid sequence
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof; wherein
Xaa1 is BE or is absent;
Xaa2 is BK, Asn or is absent;
Xaa3 is Asn, Ser or is absent;
Xaa4 is Ser or is absent;
Xaa5 is Ser, Asn, Ile, BE or is absent;
Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), Hag, or Asp;
Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
Xaa9 is Glu, Asp, Ser, Thr, or Gln;
Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
Xaa11 is Cys, Ag, or penicillamine (Pen);
Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
Xaa13 is Asn or Leu;
Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
Xaa16 is Cys, Ag, Pen or Cth;
Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
Xaa19 is Cys, Ag or Pen;
Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
Xaa21 is absent or Asn;
wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro; and
wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16 and Xaa11 and Xaa19.

### Claim 18 (depends on 17)

The peptide or pharmaceutically acceptable salt thereof according to claim 17, wherein the N-terminus is capped with acetic acid, pentenoic acid, biotin, 4-Mepip, C12 alkyl carboxylic acid, C14 alkyl carboxylic acid, C16 alkyl carboxylic acid, or C18 alkyl carboxylic acid.

### Claim 19 (depends on 17, 18)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17 or 18, wherein the C-terminus is amidated.

### Claim 20 (depends on 17, 18, 19)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-19, wherein
Xaa7 and Xaa12 are both Ag and a dicarba bond is present between Ag7 and Ag12;
Xaa7 and Xaa12 are both Cys and a disulfide bond is present between Cys7 and Cys12;
Xaa8 and Xaa16 are both Cys and a disulfide bond is present between Cys8 and Cys16;
Xaa7 is Cth and Xaa12 is Cys and a bond is present between Cth7 and Cys12;
Xaa8 is Cth and Xaa16 is Cys and a bond is present between Cth8 and Cys16;
Xaa11 and Xaa19 are Cys and a disulfide bond is present between Cys11 and Cys19; or
any combination thereof.

### Claim 21 (depends on 17, 18, 19)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-19, wherein Xaa7 is allylglycine or Cys.

### Claim 22 (depends on 17, 18, 19)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-19, wherein Xaa8 is Cys or cystathionine.

### Claim 23 (depends on 17, 18, 19, 20, 21, 22)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-22, wherein Xaa9 is Glu.

### Claim 24 (depends on 17, 18, 19, 20, 21, 22, 23)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-23, wherein Xaa10 is Leu.

### Claim 25 (depends on 17, 18, 19, 20, 21, 22, 23, 24)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-24, wherein Xaa12 is Cys or allylglycine.

### Claim 26 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-25, wherein Xaa14 is Val or Pro.

### Claim 27 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-26, wherein Xaa17 is Tyr or Thr.

### Claim 28 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-27, wherein Xaa20 is Tyr or is absent.

### Claim 29 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)

The peptide or pharmaceutically acceptable salt thereof according to any one of claims 17-28, wherein Xaa21 is absent.

### Claim 30 (depends on 17)

The peptide or pharmaceutically acceptable salt thereof according to claim 17, wherein:
Xaa1 is absent;
Xaa2 is absent;
Xaa3 is absent;
Xaa4 is absent;
Xaa5 is absent;
Xaa6 is absent;
Xaa7 is Ag, Cys, or Cth;
Xaa8 is Cys or Cth;
Xaa9 is Glu;
Xaa10 is Leu;
Xaa12 is Ag or Cys;
Xaa14 is Val or Pro;
Xaa17 is Tyr or Thr; and
Xaa20 is Tyr or is absent.

### Claim 31 (depends on 30)

The peptide or pharmaceutically acceptable salt thereof according to claim 30, wherein the peptide consists of the amino acid sequence
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 62)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
or
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH.

### Claim 32 (depends on 17)

The peptide or a pharmaceutically acceptable salt thereof according to claim 17, wherein the peptide consists of the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 3)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 4)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 5)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 6)
C14-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 7)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 8)
H-Cys Ag Glu Leu Cys Cys Asn Pro Ala Ag Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 9)
H-Asn Asp Asp Ag Glu Leu Cys Val Asn Val Ala Ag Thr Gly Cys Leu-
NH2;
(SEQ ID NO: 10)
H-Asn Asp Asp Cys Glu Leu Ag Val Asn Val Ala Cys Thr Gly Ag Leu-
NH2;
(SEQ ID NO: 11)
C18-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 12)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 13)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys-NH2;
(SEQ ID NO: 14)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 15)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 16)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 17)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 18)
H-Cys Cys Glu Leu Ag Cys Asn Pro Ala Cys Thr Gly Ag Tyr-NH2;
(SEQ ID NO: 19)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 20)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 21)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 22)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 23)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 24)
H-(4-F)Phe Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-
F)Phe-NH2;
(SEQ ID NO: 25)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 27)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 28)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys (4-F)Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 29)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu-NH2;
(SEQ ID NO: 30)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Cha-NH2;
(SEQ ID NO: 31)
H-Ag Cys Glu Cha Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 32)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys D-Tyr-NH2;
(SEQ ID NO: 33)
H-Ag Pen Glu Leu Cys Ag Asn Pro Ala Pen Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 34)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu Asn-NH2;
(SEQ ID NO: 35)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr Asn-NH2;
(SEQ ID NO: 36)
H-Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 37)
H-Ile Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-
NH2;
(SEQ ID NO: 38)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 39)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 40)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 41)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 42)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 44)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Cha Gly Cys Tyr-NH2;
(SEQ ID NO: 45)
H-Ag Cys Glu Leu Cys Ag Asn Leu Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 46)
H-Ag Cys Glu Leu Cys Ag Asn Sar Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 48)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 49)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 50)
H-Ag Cys Asp Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 51)
H-Ag Cys Ser Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 52)
H-Ag Cys Thr Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 53)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 54)
H-Ag Cys Gln Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 55)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 56)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 57)
H-Cys Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Ag-COOH;
(SEQ ID NO: 58)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 59)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 60)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 61)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 62)
H-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 63)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 65)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 66)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 67)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 72)
H-Cys Cys Glu Leu Cys Asn Val Ala Cth Tyr Gly Cys-COOH;
(SEQ ID NO: 73)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 74)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 75)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 76)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 77)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 78)
4-Mepip-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 79)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 80)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 81)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Phe Gly Cys-COOH;
(SEQ ID NO: 82)
H-Ag Ag Glu Leu Ag Ag Asn Pro Ala Ag Thr Gly Ag Tyr-COOH;
(SEQ ID NO: 83)
H-Cys Cth Glu Leu Cys Cys Asn Ala Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 84)
H-Asp Cys Glu Leu Cys Dpr Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 85)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Ser Gly Cys Tyr-NH2;
(SEQ ID NO: 86)
H-Cth Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 87)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 88)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 89)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 90)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 91)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
or
(SEQ ID NO: 92)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys-COOH.

### Claim 33

A peptide or a pharmaceutically acceptable salt thereof, wherein the peptide comprises the amino acid sequence:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Cys11 Xaa12 Asn13 Xaa14 Ala15 Cys16 Xaa17 Gly18 Cys19 Xaa20 Xaa21 (SEQ ID NO: 93), or a pharmaceutically acceptable salt thereof; wherein
Xaa1 is BE or is absent;
Xaa2 is BK or is absent;
Xaa3 is Asn or is absent;
Xaa4 is Ser or is absent;
Xaa5 is Ser, Asn, Ile, or is absent;
Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), or is absent;
Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), Hag, or Asp;
Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
Xaa9 is Glu, Asp, Ser, Thr, or Gln;
Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
Xaa12 is Cys, allylglycine (Ag), Hag, or Val;
Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, or Ala;
Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
Xaa21 is absent or Asn;
wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, or OH-Pro; and
wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Cys16, and Cys11 and Cys19.

### Claim 34 (depends on 33)

The peptide or pharmaceutically acceptable salt thereof according to claim 33, wherein the N-terminus is capped with acetic acid, pentenoic acid, 4-Mepip, C12 alkyl carboxylic acid, C14 alkyl carboxylic acid, C16 alkyl carboxylic acid, or C18 alkyl carboxylic acid.

### Claim 35 (depends on 33)

The peptide or pharmaceutically acceptable salt thereof according to claim 33, wherein the C-terminus is amidated.

### Claim 36

A pharmaceutical composition comprising a peptide or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient, diluent or carrier, wherein the peptide or pharmaceutically acceptable salt thereof comprises the amino acid sequence:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof; wherein
Xaa1 is BE or is absent;
Xaa2 is BK, Asn or is absent;
Xaa3 is Asn, Ser or is absent;
Xaa4 is Ser or is absent;
Xaa5 is Ser, Asn, Ile, BE or is absent;
Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), 4-pentenoic acid (Pent), Hag, or Asp;
Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
Xaa9 is Glu, Asp, Ser, Thr, or Gln;
Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
Xaa11 is Cys, Ag, or penicillamine (Pen);
Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
Xaa13 is Asn or Leu;
Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
Xaa16 is Cys, Ag, Pen or Cth;
Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
Xaa19 is Cys, Ag or Pen;
Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
Xaa21 is absent or Asn;
wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro; and
wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.

### Claim 37 (depends on 36)

The pharmaceutical composition according to claim 36, wherein the peptide or pharmaceutically acceptable salt thereof consists of the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 3)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 4)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 5)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 6)
C14-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 7)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 8)
H-Cys Ag Glu Leu Cys Cys Asn Pro Ala Ag Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 9)
H-Asn Asp Asp Ag Glu Leu Cys Val Asn Val Ala Ag Thr Gly Cys Leu-
NH2;
(SEQ ID NO: 10)
H-Asn Asp Asp Cys Glu Leu Ag Val Asn Val Ala Cys Thr Gly Ag Leu-
NH2;
(SEQ ID NO: 11)
C18-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 12)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 13)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys-NH2;
(SEQ ID NO: 14)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 15)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 16)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 17)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 18)
H-Cys Cys Glu Leu Ag Cys Asn Pro Ala Cys Thr Gly Ag Tyr-NH2;
(SEQ ID NO: 19)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 20)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 21)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 22)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 23)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 24)
H-(4-F)Phe Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-
F)Phe-NH2;
(SEQ ID NO: 25)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 27)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 28)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys (4-F)Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 29)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu-NH2;
(SEQ ID NO: 30)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Cha-NH2;
(SEQ ID NO: 31)
H-Ag Cys Glu Cha Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 32)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys D-Tyr-NH2;
(SEQ ID NO: 33)
H-Ag Pen Glu Leu Cys Ag Asn Pro Ala Pen Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 34)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu Asn-NH2;
(SEQ ID NO: 35)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr Asn-NH2;
(SEQ ID NO: 36)
H-Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 37)
H-Ile Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-
NH2;
(SEQ ID NO: 38)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 39)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 40)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 41)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 42)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 44)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Cha Gly Cys Tyr-NH2;
(SEQ ID NO: 45)
H-Ag Cys Glu Leu Cys Ag Asn Leu Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 46)
H-Ag Cys Glu Leu Cys Ag Asn Sar Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 48)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 49)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 50)
H-Ag Cys Asp Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 51)
H-Ag Cys Ser Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 52)
H-Ag Cys Thr Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 53)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 54)
H-Ag Cys Gln Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 55)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 56)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 57)
H-Cys Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Ag-COOH;
(SEQ ID NO: 58)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 59)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 60)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 61)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 62)
H-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 63)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 65)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 66)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 67)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 72)
H-Cys Cys Glu Leu Cys Asn Val Ala Cth Tyr Gly Cys-COOH;
(SEQ ID NO: 73)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 74)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 75)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 76)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 77)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 78)
4-Mepip-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 79)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 80)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 81)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Phe Gly Cys-COOH;
(SEQ ID NO: 82)
H-Ag Ag Glu Leu Ag Ag Asn Pro Ala Ag Thr Gly Ag Tyr-COOH;
(SEQ ID NO: 83)
H-Cys Cth Glu Leu Cys Cys Asn Ala Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 84)
H-Asp Cys Glu Leu Cys Dpr Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 85)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Ser Gly Cys Tyr-NH2;
(SEQ ID NO: 86)
H-Cth Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 87)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 88)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 89)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 90)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 91)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
or
(SEQ ID NO: 92)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys-COOH.

### Claim 38 (depends on 36)

The pharmaceutical composition according to claim 36, wherein the peptide or pharmaceutically acceptable salt thereof consists of the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 62)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
or
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH.

### Claim 39 (depends on 36, 37, 38)

The pharmaceutical composition according to any one of claims 36-38, wherein the N-terminus of the peptide is capped with acetic acid, pentenoic acid, 4-Mepip, C12 alkyl carboxylic acid, C14 alkyl carboxylic acid, C16 alkyl carboxylic acid or C18 alkyl carboxylic acid; the C-terminus of the peptide is amidated; or any combination thereof.

### Claim 40 (depends on 36, 37, 38, 39)

The pharmaceutical composition according to any one of claims 36-39, wherein the pharmaceutical composition is a solid dosage formulation.

### Claim 41 (depends on 40)

The pharmaceutical composition according to claim 40, wherein the pharmaceutical composition is formulated as an oral solid dosage formulation.

### Claim 42

A method of cleansing the colon of a subject in preparation for a colonoscopy procedure comprising administering to the subject an effective dose of a colon cleansing composition;
wherein the colon cleansing composition comprises a pharmaceutically acceptable excipient, diluent or carrier, and a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide or a pharmaceutically acceptable salt thereof comprises the amino acid sequence:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof; wherein
Xaa1 is BE or is absent;
Xaa2 is BK, Asn or is absent;
Xaa3 is Asn, Ser or is absent;
Xaa4 is Ser or is absent;
Xaa5 is Ser, Asn, Ile, BE or is absent;
Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), 4-pentenoic acid (Pent), Hag, or Asp;
Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
Xaa9 is Glu, Asp, Ser, Thr, or Gln;
Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
Xaa11 is Cys, Ag, or penicillamine (Pen);
Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
Xaa13 is Asn or Leu;
Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
Xaa16 is Cys, Ag, Pen or Cth;
Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
Xaa19 is Cys, Ag or Pen;
Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
Xaa21 is absent or Asn;
wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro; and
wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.

### Claim 43 (depends on 42)

The method according to claim 42, wherein the method further comprises:
a. orally or rectally administering to the subject an effective first dose of the colon cleansing composition; and
b. administering to the subject an effective second dose of the colon cleansing composition to substantially cleanse the colon of the subject.

### Claim 44 (depends on 43)

The method according to claim 43, wherein the effective second dose is administered the morning after the effective first dose is administered.

### Claim 45 (depends on 42)

The method according to claim 42, wherein the colon cleansing composition comprises a peptide or a pharmaceutically acceptable salt thereof comprises the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 3)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 4)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 5)
C12-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 6)
C14-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 7)
C16-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 8)
H-Cys Ag Glu Leu Cys Cys Asn Pro Ala Ag Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 9)
H-Asn Asp Asp Ag Glu Leu Cys Val Asn Val Ala Ag Thr Gly Cys Leu-
NH2;
(SEQ ID NO: 10)
H-Asn Asp Asp Cys Glu Leu Ag Val Asn Val Ala Cys Thr Gly Ag Leu-
NH2;
(SEQ ID NO: 11)
C18-BE BK Asn Ser Ser Tyr Cys Cys Glu Leu Cys Cys Asn Pro Ala Cys
Thr Gly Cys Tyr-COOH;
(SEQ ID NO: 12)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 13)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys-NH2;
(SEQ ID NO: 14)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 15)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 16)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 17)
H-Ag Cys Glu (4-F)Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 18)
H-Cys Cys Glu Leu Ag Cys Asn Pro Ala Cys Thr Gly Ag Tyr-NH2;
(SEQ ID NO: 19)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 20)
H-Ag Cys Glu Phe Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 21)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 22)
H-Cys Cys Glu (4-F)Phe Cys Cys Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-
NH2;
(SEQ ID NO: 23)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-F)Phe-NH2;
(SEQ ID NO: 24)
H-(4-F)Phe Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys (4-
F)Phe-NH2;
(SEQ ID NO: 25)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Ala Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 27)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 28)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys (4-F)Phe Gly Cys Tyr-NH2;
(SEQ ID NO: 29)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu-NH2;
(SEQ ID NO: 30)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Cha-NH2;
(SEQ ID NO: 31)
H-Ag Cys Glu Cha Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 32)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys D-Tyr-NH2;
(SEQ ID NO: 33)
H-Ag Pen Glu Leu Cys Ag Asn Pro Ala Pen Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 34)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Leu Asn-NH2;
(SEQ ID NO: 35)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr Asn-NH2;
(SEQ ID NO: 36)
H-Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 37)
H-Ile Asp Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-
NH2;
(SEQ ID NO: 38)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 39)
H-Ag Cys Glu Leu Cys Ag Asn OH-Pro Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 40)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 41)
H-Ag Cys Glu Leu Pen Ag Asn Pro Ala Cys Thr Gly Pen Tyr-NH2;
(SEQ ID NO: 42)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 44)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Cha Gly Cys Tyr-NH2;
(SEQ ID NO: 45)
H-Ag Cys Glu Leu Cys Ag Asn Leu Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 46)
H-Ag Cys Glu Leu Cys Ag Asn Sar Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 48)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Nme-Tyr-NH2;
(SEQ ID NO: 49)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 50)
H-Ag Cys Asp Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 51)
H-Ag Cys Ser Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 52)
H-Ag Cys Thr Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 53)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 54)
H-Ag Cys Gln Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 55)
H-Ag Cys Glu Leu Cys Ag Leu Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 56)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 57)
H-Cys Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Ag-COOH;
(SEQ ID NO: 58)
Pent-Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 59)
H-Hag Cys Glu Leu Cys Hag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 60)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 61)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 62)
H-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 63)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 65)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 66)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 67)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 72)
H-Cys Cys Glu Leu Cys Asn Val Ala Cth Tyr Gly Cys-COOH;
(SEQ ID NO: 73)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 74)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 75)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 76)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 77)
H-Cys Cys Glu Leu Cys Cth Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 78)
4-Mepip-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 79)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 80)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-NH2;
(SEQ ID NO: 81)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Phe Gly Cys-COOH;
(SEQ ID NO: 82)
H-Ag Ag Glu Leu Ag Ag Asn Pro Ala Ag Thr Gly Ag Tyr-COOH;
(SEQ ID NO: 83)
H-Cys Cth Glu Leu Cys Cys Asn Ala Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 84)
H-Asp Cys Glu Leu Cys Dpr Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 85)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Ser Gly Cys Tyr-NH2;
(SEQ ID NO: 86)
H-Cth Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 87)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 88)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 89)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys-COOH;
(SEQ ID NO: 90)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 91)
H-Cth Cys Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
or
(SEQ ID NO: 92)
H-Cys Cys Glu Leu Cys Cys Asn Val Ala Cth Tyr Gly Cys-COOH.

### Claim 46 (depends on 42)

The method according to claim 42, wherein the colon cleansing composition comprises a peptide or a pharmaceutically acceptable salt thereof comprises the amino acid sequence:
(SEQ ID NO: 2)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 26)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 43)
H-Ag Cys Glu Leu Cys Ag Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 47)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Thr Gly Cys Tyr-NH2;
(SEQ ID NO: 62)
H-Ag Cys Glu Leu Cys Ag Asn Val Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 64)
H-Cth Cys Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 68)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys Tyr-NH2;
(SEQ ID NO: 69)
Ac-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
(SEQ ID NO: 70)
H-Cys Cth Glu Leu Cys Cys Asn Val Ala Cys Tyr Gly Cys-COOH;
or
(SEQ ID NO: 71)
Ac-Cys Cth Glu Leu Cys Cys Asn Pro Ala Cys Tyr Gly Cys-COOH.

### Claim 47 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of producing the peptide of any one of claims 1-35, comprising providing a cell harboring a nucleic acid molecule encoding the polypeptide, culturing the cell under conditions in which the peptide is expressed, and isolating the expressed peptide.

### Claim 48 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of producing the peptide of any of claims 1-35, comprising chemically synthesizing the peptide and purifying the synthesized peptide.

### Claim 49 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of treating a gastrointestinal or visceral disorder comprising administering to a subject a peptide of any of claims 1-35.

### Claim 50 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A method of treating a disorder selected from colon cancer, Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Lynch syndrome, gastroparesis (GP), polyps, pain, general abdominal pain, post-operative ileus, opioid-induced constipation, functional dyspepsia, diverticular disease including including but not limited to SUDD (symptomatic uncomplicated diverticular disease) and SCAD (segmental colitis associated with diverticulosis), diverticulosis, diarrhea-predominant irritable bowel syndrome, pain associated with irritable bowel syndrom (IBS), ulcerative colitis, ulcerative proctitis, Crohn's Disease, inflammatory bowel disease (IBD), chronic or acute radiation protopathy, rectal pain, chronic proctalgia, proctalgia fugax, anal pain, chronic anal fissure, post-operative anal pain, overactive bladder syndrome, stress incontinence, interstitial cystitis, bladder pain syndrome, colorectal cancer, pain associated with cancer, general pelvic pain, endometriosis, orchialgia, chronic prostatitis, prostatodynia, vulvodynia, urethral syndrome, penile pain, perianal pain and other gastrointestinal and visceral disorders, comprising administering to a subject a peptide of any of claims 1-35.

### Claim 51 (depends on 51)

The method of claim 51, further comprising administering to the subject a pharmaceutical composition comprising an active ingredient selected from opioids, tramadol, beta-3 adrenergic receptor agonists, anti-cholinergic agents, and tricyclic antidepressants.

### Claim 52

A pharmaceutical composition for use in cleansing the colon in a subject in preparation for a colonoscopy procedure, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient, diluent or carrier, and a peptide or a pharmaceutically acceptable salt thereof, wherein the peptide or a pharmaceutically acceptable salt thereof comprises the amino acid sequence:
Xaa1 Xaa2 Xaa3 Xaa4 Xaa5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13 Xaa14 Ala15 Xaa16 Xaa17 Gly18 Xaa19 Xaa20 Xaa21 (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof; wherein
Xaa1 is BE or is absent;
Xaa2 is BK, Asn or is absent;
Xaa3 is Asn, Ser or is absent;
Xaa4 is Ser or is absent;
Xaa5 is Ser, Asn, Ile, BE or is absent;
Xaa6 is Tyr, Asp, 4-fluorophenylalanine ((4-F)Phe), BK or is absent;
Xaa7 is Cys, cystathionine (Cth), allylglycine (Ag), 4-pentenoic acid (Pent), Hag, or Asp;
Xaa8 is Cys, cystathionine (Cth), penicillamine (Pen), or allylglycine (Ag);
Xaa9 is Glu, Asp, Ser, Thr, or Gln;
Xaa10 is Leu, cyclohexylalanine (Cha), Phe, or 4-fluorophenylalanine ((4-F)Phe);
Xaa11 is Cys, Ag, or penicillamine (Pen);
Xaa12 is Cys, allylglycine (Ag), Hag, Cth, Dpr, or Val;
Xaa13 is Asn or Leu;
Xaa14 is Pro, Val, sarcosine (Sar), Leu, or Hydroxyproline (OH-Pro);
Xaa16 is Cys, Ag, Pen or Cth;
Xaa17 is Tyr, Thr, cyclohexylalanine (Cha), 4-fluorophenylalanine ((4-F)Phe), Phe, Ser, or Ala;
Xaa19 is Cys, Ag or Pen;
Xaa20 is Tyr, Leu, 4-fluorophenylalanine ((4-F)Phe), cyclohexylalanine (Cha), D-Tyr, N-Methyl Tyr (Nme-Tyr) or is absent;
Xaa21 is absent or Asn;
wherein at least one Xaa is BE, BK, (4-F)Phe, Cth, Ag, Hag, Pen, Cha, Sar, Dpr, or OH-Pro; and
wherein the peptide contains a covalent bond between Xaa7 and Xaa12, Xaa8 and Xaa16, and Xaa11 and Xaa19.

### Claim 53 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A pharmaceutical composition for use in treating a disorder selected from colon cancer, Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Lynch syndrome, gastroparesis (GP), polyps, pain, general abdominal pain, post-operative ileus, opioid-induced constipation, functional dyspepsia, diverticular disease including including but not limited to SUDD (symptomatic uncomplicated diverticular disease) and SCAD (segmental colitis associated with diverticulosis), diverticulosis, diarrhea-predominant irritable bowel syndrome, pain associated with irritable bowel syndrom (IBS), ulcerative colitis, ulcerative proctitis, Crohn's Disease, inflammatory bowel disease (IBD), chronic or acute radiation protopathy, rectal pain, chronic proctalgia, proctalgia fugax, anal pain, chronic anal fissure, post-operative anal pain, overactive bladder syndrome, stress incontinence, interstitial cystitis, bladder pain syndrome, colorectal cancer, pain associated with cancer, general pelvic pain, endometriosis, orchialgia, chronic prostatitis, prostatodynia, vulvodynia, urethral syndrome, penile pain, perianal pain and other gastrointestinal and visceral disorders, and
wherein the pharmaceutical composition comprises a peptide of any of claims 1-35.