Stapled antimicrobial peptides (stamps) and uses thereof
AssigneeLytica Therapeutics, Inc.
InventorsRida Mourtada, Daniel T. Cohen
Life of this patent
Estimating the term…
Abstract
Provided are stapled antimicrobial peptides (i.e., StAMPs), including cysteine-stapled antimicrobial peptides (i.e., C-StAMPs), and methods of using the same (e.g., for treating bacterial infections caused by Gram-negative bacteria). In certain embodiments, the stapled peptides are based on the amino acid sequence of the antimicrobial peptide Esculentin-1A and comprise one or more dithio staples. Also provided are unstapled peptides which can serve as synthetic precursors to the stapled peptides provided herein.
Claims96
A peptide, or a pharmaceutically acceptable salt thereof, comprising 10 or more contiguous amino acids of Esculentin-1A and comprising exactly one internal crosslink connecting two crosslinked amino acids, wherein:
- two amino acids of the 10 or more contiguous amino acids of Esculentin-1A are independently substituted by X1 and X2;
- and
- X1 and X2 are independently the crosslinked amino acids;
- optionally wherein the amino acid sequence includes 1 to 3 amino acid substitutions, inclusive, at positions other than X1 and X2.
A peptide, or a pharmaceutically acceptable salt thereof, comprising 10 or more contiguous amino acids of Esculentin-1A;
- wherein:
- exactly two amino acids of the 10 or more contiguous amino acids of Esculentin-1A are independently substituted by X1 and X2;
- and
- X1 and X2 are each independently amino acids comprising reactive moieties capable of forming a crosslink with the other;
- optionally wherein the amino acid sequence includes 1 to 3 amino acid substitutions, inclusive, at positions other than X1 and X2.
A peptide comprising the amino acid sequence:
- (SEQ ID NO:
- 32)
- G I F S KL X1 G K K X2 K N L L I X3 G L K X4,
- or a pharmaceutically acceptable salt thereof, wherein:
- X1, X2, X3, and X4 are independently amino acids;
- X1 and X2 are connected via a crosslink, and X3 and X4 are connected via a crosslink;
- and
- optionally wherein the amino acid sequence includes 1 to 6 amino acid substitutions, inclusive, at positions other than X1, X2, X3, and X4.
A peptide comprising the amino acid sequence SEQ ID NO:
- 32, or a pharmaceutically acceptable salt thereof, wherein:
- X1, X2, X3, and X4 are independently amino acids;
- X1 and X2 each independently comprise a reactive moiety capable of forming a crosslink with the other, and X3 and X4 each independently comprise a reactive moiety capable of forming a crosslink with the other;
- and
- the amino acid sequence includes 1 to 6 amino acid substitutions, inclusive, at positions other than X1, X2, X3, and X4.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the crosslinks are attached to the α-positions of the amino acids X1, X2, X3, and X4.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each crosslink is independently optionally substituted alkylene, optionally substituted alkenylene, optionally substituted alkynylene, optionally substituted heteroalkylene, optionally substituted heteroalkenylene, optionally substituted heteroalkynylene, optionally substituted carbocyclylene, optionally substituted heterocyclylene, optionally substituted arylene, optionally substituted heteroarylene, optionally substituted acylene, or any combination thereof.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each crosslink is independently a dithio crosslink.
A peptide, or a pharmaceutically acceptable salt thereof, comprising 10 or more contiguous amino acids of Esculentin-1A and at least one internal dithio crosslink, wherein:
- at least 2 amino acids of the 10 or more contiguous amino acids of Esculentin-1A are substituted by a pair of dithio-crosslinked amino acids;
- optionally wherein the amino acid sequence includes 1 to 3 additional amino acid substitutions, inclusive.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each crosslink is independently of one of the following formulae:
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein each crosslink is independently about 5 Å to about 35 Å in length, inclusive.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the length of each crosslink is approximately equal to the length of 5 to 25 carbon-carbon and/or carbon-sulfur bonds, inclusive.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one crosslink spans an α-helix of the peptide.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein at least one crosslink stabilizes an α-helix of the peptide.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the peptide has increased α-helicity as compared to a corresponding uncrosslinked peptide.
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the peptide comprises one of the following peptides:
- StAMP
- SEQ ID
- X1-X2
- C-
- #
- Sequence
- NO:
- Crosslink
- terminus
- 1
- G
- I
- X1
- S
- K
- L
- X2
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 3
- but
- —NH2
- 2
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 7
- mxy
- —NH2
- 3
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 7
- pxy
- —NH2
- 4
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 7
- but
- —NH2
- 5
- G
- I
- F
- X1
- K
- L
- A
- X2
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 4
- mxy
- —NH2
- 6
- G
- I
- F
- X1
- K
- L
- A
- X2
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 4
- pxy
- —NH2
- 7
- G
- I
- F
- X1
- K
- L
- A
- X2
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 4
- but
- —NH2
- 8
- G
- I
- F
- S
- K
- X1
- A
- G
- K
- X2
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 6
- pxy
- —NH2
- 9
- G
- I
- F
- S
- K
- X1
- A
- G
- K
- X2
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 6
- but
- —NH2
- 10
- G
- I
- F
- S
- K
- L
- A
- X1
- K
- K
- I
- X2
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 8
- mxy
- —NH2
- 11
- G
- I
- F
- S
- K
- L
- A
- X1
- K
- K
- I
- X2
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 8
- pxy
- —NH2
- 12
- G
- I
- F
- S
- K
- L
- A
- X1
- K
- K
- I
- X2
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 8
- but
- —NH2
- 13
- G
- I
- F
- S
- K
- L
- A
- G
- X1
- K
- I
- K
- X2
- L
- L
- I
- S
- G
- L
- K
- G
- 9
- pxy
- —NH2
- 14
- G
- I
- F
- S
- K
- L
- A
- G
- K
- X1
- I
- K
- N
- X2
- L
- I
- S
- G
- L
- K
- G
- 10
- mxy
- —NH2
- 15
- G
- I
- F
- S
- K
- L
- A
- G
- K
- X1
- I
- K
- N
- X2
- L
- I
- S
- G
- L
- K
- G
- 10
- pxy
- —NH2
- 16
- G
- I
- F
- S
- K
- L
- A
- G
- K
- X1
- I
- K
- N
- X2
- L
- I
- S
- G
- L
- K
- G
- 10
- but
- —NH2
- 17
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- X1
- K
- N
- L
- X2
- I
- S
- G
- L
- K
- G
- 11
- mxy
- —NH2
- 18
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- X1
- K
- N
- L
- X2
- I
- S
- G
- L
- K
- G
- 11
- pxy
- —NH2
- 19
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- X1
- K
- N
- L
- X2
- I
- S
- G
- L
- K
- G
- 11
- but
- —NH2
- 20
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- X1
- N
- L
- L
- X2
- S
- G
- L
- K
- G
- 12
- mxy
- —NH2
- 21
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- X1
- N
- L
- L
- X2
- S
- G
- L
- K
- G
- 12
- pxy
- —NH2
- 22
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- X1
- N
- L
- L
- X2
- S
- G
- L
- K
- G
- 12
- but
- —NH2
- 23
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- X1
- L
- L
- I
- X2
- G
- L
- K
- G
- 13
- mxy
- —NH2
- 24
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- X1
- L
- L
- I
- X2
- G
- L
- K
- G
- 13
- pxy
- —NH2
- 25
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- X1
- L
- L
- I
- X2
- G
- L
- K
- G
- 13
- but
- —NH2
- 26
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- X1
- L
- I
- S
- X2
- L
- K
- G
- 14
- mxy
- —NH2
- 27
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- X1
- L
- I
- S
- X2
- L
- K
- G
- 14
- pxy
- —NH2
- 28
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- X1
- L
- I
- S
- X2
- L
- K
- G
- 14
- but
- —NH2
- 29
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- X1
- I
- S
- G
- X2
- K
- G
- 15
- mxy
- —NH2
- 30
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- X1
- I
- S
- G
- X2
- K
- G
- 15
- pxy
- —NH2
- 31
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- X1
- I
- S
- G
- X2
- K
- G
- 15
- but
- —NH2
- 32
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- X1
- S
- G
- L
- X2
- G
- 16
- mxy
- —NH2
- 33
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- X1
- S
- G
- L
- X2
- G
- 16
- pxy
- —NH2
- 34
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- X1
- S
- G
- L
- X2
- G
- 16
- but
- —NH2
- 35
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- X1
- G
- L
- K
- X2
- 17
- but
- —NH2
- 36
- X1
- I
- F
- S
- X2
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 1
- mxy
- —NH2
- 37
- X1
- I
- F
- S
- X2
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 1
- pxy
- —NH2
- 38
- X1
- I
- F
- S
- X2
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 1
- but
- —NH2
- 39
- G
- I
- X1
- S
- K
- L
- X2
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 3
- mxy
- —NH2
- 40
- G
- I
- X1
- S
- K
- L
- X2
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 3
- pxy
- —NH2
- 41
- G
- I
- F
- S
- K
- X1
- A
- G
- K
- X2
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 6
- mxy
- —NH2
- 42
- G
- I
- F
- S
- K
- L
- A
- G
- X1
- K
- I
- K
- X2
- L
- L
- I
- S
- G
- L
- K
- G
- 9
- mxy
- —NH2
- 43
- G
- I
- F
- S
- K
- L
- A
- G
- X1
- K
- I
- K
- X2
- L
- L
- I
- S
- G
- L
- K
- G
- 9
- but
- —NH2
- 44
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- X1
- G
- L
- K
- X2
- 17
- mxy
- —NH2
- 45
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- X1
- G
- L
- K
- X2
- 17
- pxy
- —NH2
- 46
- G
- X1
- F
- S
- K
- X2
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 2
- mxy
- —NH2
- 47
- G
- X1
- F
- S
- K
- X2
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 2
- pxy
- —NH2
- 48
- G
- X1
- F
- S
- K
- X2
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 2
- but
- —NH2
- 91
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 7
- mxy
- —CO2H
- 92
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- G
- G
- 74
- mxy
- —CO2H
- 93
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- G
- G
- G
- 65
- mxy
- —CO2H
- 94
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- G
- G
- K
- 66
- mxy
- —CO2H
- 95
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- A
- G
- 67
- mxy
- —CO2H
- 96
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- A
- K
- 68
- mxy
- —CO2H
- 97
- G
- I
- F
- S
- K
- L
- X1
- A
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 69
- mxy
- —CO2H
- 98
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- A
- L
- K
- G
- 70
- mxy
- —CO2H
- 99
- G
- I
- F
- S
- K
- L
- X1
- A
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 77
- mxy
- —CO2H
- 100
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- A
- K
- 68
- but
- —CO2H
- 101
- J
- I
- F
- S
- K
- X2
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 78
- but
- —CO2H
- 102
- J
- I
- F
- S
- K
- X2
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 78
- but
- —NH2
- 103
- J
- I
- F
- S
- K
- X2
- A
- G
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 78
- but
- —NHOH
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the peptide comprises one of the following peptides:
- StAMP
- SEQ
- X1-X2
- C-
- #
- Sequence
- ID NO:
- Crosslink
- terminus
- 49
- X1
- I
- F
- S
- K
- L
- A
- X2
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 18
- bbp
- —NH2
- 50
- X1
- I
- F
- S
- K
- L
- A
- X2
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 18
- bbn
- —NH2
- 51
- X1
- I
- F
- S
- K
- L
- A
- X2
- K
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 18
- bbf
- —NH2
- 52
- G
- X1
- F
- S
- K
- L
- A
- G
- X2
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 19
- bbn
- —NH2
- 53
- G
- X1
- F
- S
- K
- L
- A
- G
- X2
- K
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 19
- bbf
- —NH2
- 54
- G
- I
- X1
- S
- K
- L
- A
- G
- K
- X2
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 20
- bbp
- —NH2
- 55
- G
- I
- X1
- S
- K
- L
- A
- G
- K
- X2
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 20
- bbn
- —NH2
- 56
- G
- I
- X1
- S
- K
- L
- A
- G
- K
- X2
- I
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 20
- bbf
- —NH2
- 57
- G
- I
- F
- X1
- K
- L
- A
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 21
- bbp
- —NH2
- 58
- G
- I
- F
- X1
- K
- L
- A
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 21
- bbn
- —NH2
- 59
- G
- I
- F
- X1
- K
- L
- A
- G
- K
- K
- X2
- K
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 21
- bbf
- —NH2
- 60
- G
- I
- F
- S
- X1
- L
- A
- G
- K
- K
- I
- X2
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 22
- bbp
- —NH2
- 61
- G
- I
- F
- S
- X1
- L
- A
- G
- K
- K
- I
- X2
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 22
- bbf
- —NH2
- 62
- G
- I
- F
- S
- X1
- L
- A
- G
- K
- K
- I
- X2
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 22
- bbn
- —NH2
- 63
- G
- I
- F
- S
- K
- X1
- A
- G
- K
- K
- I
- K
- X2
- L
- L
- I
- S
- G
- L
- K
- G
- 23
- bbp
- —NH2
- 64
- G
- I
- F
- S
- K
- X1
- A
- G
- K
- K
- I
- K
- X2
- L
- L
- I
- S
- G
- L
- K
- G
- 23
- bbn
- —NH2
- 65
- G
- I
- F
- S
- K
- X1
- A
- G
- K
- K
- I
- K
- X2
- L
- L
- I
- S
- G
- L
- K
- G
- 23
- bbf
- —NH2
- 66
- G
- I
- F
- S
- K
- L
- A
- X1
- K
- K
- I
- K
- N
- L
- X2
- I
- S
- G
- L
- K
- G
- 24
- bbp
- —NH2
- 67
- G
- I
- F
- S
- K
- L
- A
- X1
- K
- K
- I
- K
- N
- L
- X2
- I
- S
- G
- L
- K
- G
- 24
- bbn
- —NH2
- 68
- G
- I
- F
- S
- K
- L
- A
- X1
- K
- K
- I
- K
- N
- L
- X2
- I
- S
- G
- L
- K
- G
- 24
- bbf
- —NH2
- 69
- G
- I
- F
- S
- K
- L
- A
- G
- X1
- K
- I
- K
- N
- L
- L
- X2
- S
- G
- L
- K
- G
- 25
- bbn
- —NH2
- 70
- G
- I
- F
- S
- K
- L
- A
- G
- X1
- K
- I
- K
- N
- L
- L
- X2
- S
- G
- L
- K
- G
- 25
- bbf
- —NH2
- 71
- G
- I
- F
- S
- K
- L
- A
- G
- X1
- K
- I
- K
- N
- L
- L
- X2
- S
- G
- L
- K
- G
- 25
- bbp
- —NH2
- 72
- G
- I
- F
- S
- K
- L
- A
- G
- K
- X1
- I
- K
- N
- L
- L
- I
- X2
- G
- L
- K
- G
- 26
- bbp
- —NH2
- 73
- G
- I
- F
- S
- K
- L
- A
- G
- K
- X1
- I
- K
- N
- L
- L
- I
- X2
- G
- L
- K
- G
- 26
- bbn
- —NH2
- 74
- G
- I
- F
- S
- K
- L
- A
- G
- K
- X1
- I
- K
- N
- L
- L
- I
- X2
- G
- L
- K
- G
- 26
- bbf
- —NH2
- 75
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- X1
- K
- N
- L
- L
- I
- S
- X2
- L
- K
- G
- 27
- bbn
- —NH2
- 76
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- X1
- K
- N
- L
- L
- I
- S
- X2
- L
- K
- G
- 27
- bbf
- —NH2
- 77
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- X1
- K
- N
- L
- L
- I
- S
- X2
- L
- K
- G
- 27
- bbp
- —NH2
- 78
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- X1
- N
- L
- L
- I
- S
- G
- X2
- K
- G
- 28
- bbn
- —NH2
- 79
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- X1
- N
- L
- L
- I
- S
- G
- X2
- K
- G
- 28
- bbf
- —NH2
- 80
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- C
- N
- L
- L
- I
- S
- G
- L
- K
- G
- 28
- bbp
- —NH2
- 81
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- X1
- L
- L
- I
- S
- G
- L
- X2
- G
- 29
- bbp
- —NH2
- 82
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- X1
- L
- L
- I
- S
- G
- L
- X2
- G
- 29
- bbn
- —NH2
- 83
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- X1
- L
- L
- I
- S
- G
- L
- X2
- G
- 29
- bbf
- —NH2
- 84
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- X1
- L
- I
- S
- G
- L
- K
- X2
- 30
- bbp
- —NH2
- 85
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- X1
- L
- I
- S
- G
- L
- K
- X2
- 30
- bbn
- —NH2
- 86
- G
- I
- F
- S
- K
- L
- A
- G
- K
- K
- I
- K
- N
- X1
- L
- I
- S
- G
- L
- K
- X2
- 30
- bbf
- —NH2
- 87
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- I
- K
- N
- X2
- L
- I
- S
- G
- L
- K
- G
- 31
- bbn
- —NH2
- 88
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- I
- K
- N
- X2
- L
- I
- S
- G
- L
- K
- G
- 31
- bbf
- —NH2
- 89
- G
- I
- F
- S
- K
- L
- X1
- G
- K
- K
- I
- K
- N
- X2
- L
- I
- S
- G
- L
- K
- G
- 31
- bbp
- —NH2
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the peptide comprises on of the following peptides:
- SEQ
- X1-X2 and
- StAMP
- ID
- X3-X4
- C-
- #
- Sequence
- NO:
- Crosslink
- terminus
- 90
- G I F S K L X1 G K K X2 K N L L I X3 G L K X4
- 32
- pxy
- —NH2
The peptide of any one of the preceding claims, or a pharmaceutically acceptable salt thereof, wherein the reactive moieties are thiols.
A peptide, or a pharmaceutically acceptable salt thereof, comprising 10 or more contiguous amino acids of Esculentin-1A, wherein:
- 2 or 4 amino acids of the 10 or more contiguous amino acids of Esculentin are substituted by C;
- optionally wherein the amino acid sequence includes 1 to 6 additional amino acid substitutions, inclusive.
A peptide of any one of the preceding claims, wherein the peptide comprises one of the following amino acid sequences:
- (SEQ ID NO:
- 37)
- C I F S C L A G K K I K N L L I S G L K G,
- (SEQ ID NO:
- 38)
- G C F S K C A G K K I K N L L I S G L K G,
- (SEQ ID NO:
- 39)
- G I C S K L C G K K I K N L L I S G L K G,
- (SEQ ID NO:
- 40)
- G I F C K L A C K K I K N L L I S G L K G,
- (SEQ ID NO:
- 41)
- G I F S C L A G C K I K N L L I S G L K G,
- (SEQ ID NO:
- 42)
- G I F S K C A G K C I K N L L I S G L K G,
- (SEQ ID NO:
- 43)
- G I F S K L C G K K C K N L L I S G L K G,
- (SEQ ID NO:
- 82)
- G I F S K L C G K K C K N L L I S G L K G G G,
- (SEQ ID NO:
- 44)
- G I F S K L A C K K I C N L L I S G L K G,
- (SEQ ID NO:
- 45)
- G I F S K L A G C K I K C L L I S G L K G,
- (SEQ ID NO:
- 46)
- G I F S K L A G K C I K N C L I S G L K G,
- (SEQ ID NO:
- 47)
- G I F S K L A G K K C K N L C I S G L K G,
- (SEQ ID NO:
- 48)
- G I F S K L A G K K I C N L L C S G L K G,
- (SEQ ID NO:
- 49)
- G I F S K L A G K K I K C L L I C G L K G,
- (SEQ ID NO:
- 50)
- G I F S K L A G K K I K N C L I S C L K G,
- (SEQ ID NO:
- 51)
- G I F S K L A G K K I K N L C I S G C K G,
- (SEQ ID NO:
- 52)
- G I F S K L A G K K I K N L L C S G L C G,
- (SEQ ID NO:
- 53)
- G I F S K L A G K K I K N L L I C G L K C,
- (SEQ ID NO:
- 79)
- G I F S K L C G K K C K N L L I S G L K G G G G,
- (SEQ ID NO:
- 80)
- G I F S K L C G K K C K N L L I S G L K G G G K,
- (SEQ ID NO:
- 81)
- G I F S K L C G K K C K N L L I S G L K G A G,
- (SEQ ID NO:
- 83)
- G I F S K L C G K K C K N L L I S G L K G A K,
- (SEQ ID NO:
- 84)
- G I F S K L C A K K C K N L L I S G L K G,
- (SEQ ID NO:
- 85)
- G I F S K L C G K K C K N L L I S A L K G,
- (SEQ ID NO:
- 86)
- G I F S K L C A K K C K N L L I S A L K G,
- (SEQ ID NO:
- 87)
- JIFSKCAGKCIKNLLISGLKG,
- or a pharmaceutically acceptable salt thereof.
The peptide of any one of the preceding claims, wherein the peptide comprises one of the following amino acid sequences:
- (SEQ ID NO:
- 55)
- G C F S K L A G C K I K N L L I S G L K G,
- (SEQ ID NO:
- 56)
- G I C S K L A G K C I K N L L I S G L K G,
- (SEQ ID NO:
- 57)
- G I F C K L A G K K C K N L L I S G L K G,
- (SEQ ID NO:
- 58)
- G I F S C L A G K K I C N L L I S G L K G,
- (SEQ ID NO:
- 59)
- G I F S K C A G K K I K C L L I S G L K G,
- (SEQ ID NO:
- 60)
- G I F S K L A C K K I K N L C I S G L K G,
- (SEQ ID NO:
- 61)
- G I F S K L A G C K I K N L L C S G L K G,
- (SEQ ID NO:
- 62)
- G I F S K L A G K C I K N L L I C G L K G,
- (SEQ ID NO:
- 63)
- G I F S K L A G K K C K N L L I S C L K G,
- (SEQ ID NO:
- 64)
- G I F S K L A G K K I C N L L I S G C K G,
- (SEQ ID NO:
- 65)
- G I F S K L A G K K I K C L L I S G L C G,
- (SEQ ID NO:
- 66)
- G I F S K L A G K K I K N C L I S G L K C,
- (SEQ ID NO:
- 67)
- G I F S K L C G K K I K N C L I S G L K G,
- or a pharmaceutically acceptable salt thereof.
The peptide of any one of the preceding claims, wherein the peptide comprises the following amino acid sequence:
- (SEQ ID NO:
- 68)
- G I F S K L C G K K C K N L L I C G L K C,
- or a pharmaceutically acceptable salt thereof.
A method of preparing a crosslinked peptide of any one of the preceding claims comprising a step of reacting an uncrosslinked peptide of any one of the preceding claims under conditions sufficient to form the crosslinks connecting X1 and X2, and X3 and X4.
Dependencies are inferred from the claim text.