LHRH antagonist peptides
AssigneeIndiana University Research and Technology Corporation
InventorRoger W. Roeske
Life of this patent
Estimating the term…
Abstract
Novel LHRH antagonist peptides, pharmaceutical compositions thereof, and methods of use thereof, are disclosed. The LHRH antagonist comprise a peptide compound, wherein a residue of the peptide compound corresponding to the amino acid at position 6 of natural mammalian LHRH comprises a hydrophilic N-acyl moiety, a dipolar moiety, a sulfonium moiety, a receptor-modifying moiety or a small polar moiety.
Claims14
A method of rejuvenating the thymus in a subject, comprising administering to the subject an effective amount of a peptide compound which inhibits LHRH activity, wherein the peptide compound comprises a structure:
- A-B-C-D-E-F-G-H-I-J
- wherein
- A is pyro-Glu, Ac-D-Nal , Ac-D-Qal, Ac-Sar, or Ac-D-Pal;
- B is His or 4-Cl-D-Phe;
- C is Trp, D-Pal, D-Nal, L-Nal, D-Pal(N—O), or D-Trp;
- D is Ser;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile;
- F is D-Asn or D-Gln;
- G is Leu or Trp;
- H is Lys(iPr), Gin, Met, or Arg;
- I is Pro;
- and
- J is Gly-NH2 or D-Ala-NH2;
- or a pharmaceutically acceptable salt thereof, thereby rejuvenating the thymus in the subject.
A method of rejuvenating the thymus in a subject comprising administering to the subject an effective amount of a peptide compound which inhibits LHRH activity, wherein the peptide compound comPrises a structure:
- A-B-C-D-E-F-G-H-I-J
- wherein
- A is pyro-Glu, Ac-D-Nal , Ac-D-Qal, Ac-Sar, or Ac-D-Pal;
- B is His or 4-Cl-D-Phe;
- C is Trp, D-Pal, D-Nal, L-Nal, D-Pal(N—O), or D-Trp;
- D is Ser;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile;
- F is D-Asn;
- G is Leu or Trp;
- H is Lys(iPr), Gin, Met, or Arg;
- I is Pro;
- and
- J is Gly-NH2 or D-Ala-NH2;
- or a pharmaceutically acceptable salt thereof, thereby rejuvenating the thymus in the subject.
A method of rejuvenating the thymus in a subject, comprising administering to a subject an effective amount of a peptide compound which inhibits LHR.H activity, wherein the peptide compound comprises a structure:
- A-B-C-D-E-F-G-H-I-J
- wherein
- A is pyro-Glu, Ac-Nal , Ac-Qal, Ac-Sar, or Ac-Pal, or an analogue thereof;
- B is His or 4-Cl-Phe, or an analogue thereof;
- C is Trp, Pal, Nal, Nal-Pal(N—O), or Trp, or an analogue thereof;
- D is Ser, or an analogue thereof;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile, or an analogue thereof;
- F is Asn or Gln;
- G is Leu or Trp, or an analogue thereof;
- H is Lys(iPr), Gln, Met, or Arg, or an analogue thereof;
- I is Pro, or an analogue thereof;
- and
- J is Gly-NH2 or Ala-NH2, or an analogue thereof;
- or a pharmaceutically acceptable salt thereof, thereby rejuvenating the thymus in the subject.
A method of rejuvenating the thymus in a subject, comprising administering to a subject an effective amount of a peptide compound which inhibits LHRH activity, wherein the peptide compound comprises a structure:
- A-B-C-D-E-F-G-H-I
- wherein
- A is pyro-Glu, Ac-Nal , Ac-Qal, Ac-Sar, or Ac-Pal, or an analogue thereof;
- B is His or 4-Cl-Phe, or an analogue thereof;
- C is Trp, Pal, Nal, Nal-Pal(N—O), or Trp, or an analogue thereof;
- D is Ser, or an analogue thereof;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Arg or Ile, or an analogue thereof;
- F is Asn or Gln;
- G is Leu or Trp, or an analogue thereof;
- H is Lys(iPr), Gln, Met, or Arg, or an analogue thereof;
- and
- I is Pro, or an analogue thereof;
- or a pharmaceutically acceptable salt thereof, thereby rejuvenating the thymus in the subject.
A method of rejuvenating the thymus in a subject, comprising administering to a subject an effective amount of a peptide compound which inhibits LHRH activity, wherein the peptide compound comprises a structure:
- A-B-C-D-E-F-G-H-I
- wherein
- A is pyro-Glu, Ac-D-Nal , Ac-D-Qal, Ac-Sar, or Ac-D-Pal, or an analogue thereof;
- B is His or 4-Cl-D-Phe, or an analogue thereof;
- C is Trp, D-Pal, D-Nal, L-Nal-D-Pal(N—O), or D-Trp, or an analogue thereof;
- D is Ser, or an analogue thereof;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Mg or Ile, or an analogue thereof;
- F is D-Asn or D-Gln;
- G is Leu or Trp, or an analogue thereof;
- H is Lys(iPr), Gln, Met, or Arg, or an analogue thereof;
- and
- I is Pro, or an analogue thereof;
- or a pharmaceutically acceptable salt thereof, thereby rejuvenating the thymus in the subject.
A method of stimulating the production of T cells in a subject, comprising administering to the subject an effective amount of a peptide compound which inhibits LHRH activity, wherein the peptide compound comprises a structure:
- A-B-C-D-E-F-G-H-I-J
- wherein
- A is pyro-Glu, Ac-D-Nal , Ac-D-Qal, Ac-Sar, or Ac-D-Pal;
- B is His or 4-Cl-D-Phe;
- C is Trp, D-Pal, D-Nal, L-Nal-D-Pal(N—O), or D-Trp;
- D is Ser;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Mg or Ile;
- F is D-Asn or D-Gln;
- G is Leu or Trp;
- H is Lys(iPr), Gln, Met, or Arg;
- I is Pro;
- and
- J is Gly-NH2 or D-Ala-NH2;
- or a pharmaceutically acceptable salt thereof, thereby stimulating the production of T cells in the subject.
A method of stimulating the production of T cells in a subject, comprising administering to the subject an effective amount of a peptide compound which inhibits LHRH activity, wherein the peptide compound comprises a structure:
- A-B-C-D-E-F-G-H-I-J
- wherein
- A is pyro-Glu, Ac-D-Nal , Ac-D-Qal, Ac-Sar, or Ac-D-Pal;
- B is His or 4-Cl-D-Phe;
- C is Trp, D-Pal, D-Nal, L-Nal-D-Pal(N—O), or D-Trp;
- D is Ser;
- E is N-Me-Ala, Tyr, N-Me-Tyr, Ser, Lys(iPr), 4-Cl-Phe, His, Asn, Met, Ala, Mg or Ile;
- F is D-Asn;
- G is Leu or Trp;
- H is Lys(iPr), Gln, Met, or Arg;
- I is Pro;
- and
- J is Gly-NH2 or D-Ala-NH2;
- or a pharmaceutically acceptable salt thereof, thereby stimulating the production of T cells in the subject.
Dependencies are inferred from the claim text.