Melanin-concentrating hormone antagonists
View Patent ↗The present invention features MCH antagonists active at the MCH-1R. The antagonists are optionally modified peptides able to inhibit the effect of MCH at MCH-1R. MCH antagonists have a variety of uses including being used as a research tool and being used to achieve a beneficial effect in a subject.
1. An optionally labeled peptide having the structure:
wherein Gva is des-amino-arginine
XAA 1 is either methionine or norleucine;
XAA 2 is either glycine or D-norleucine;
XAA 3 is valine or alanine;
Ava is 5-aminovaleric acid; and
Z 2 is an optionally present protecting group that, if present, is covalently joined to the C-terminal carboxy group;
or a pharmaceutically acceptable salt of said peptide;
wherein said peptide is optionally labeled with a detectable label selected from the group consisting of: luminescent, enzymatic and radioactive.
2. The peptide of claim 1 , where said peptide consists of the structure:
wherein Gva is des-amino-arginine;
XAA 1 is either methionine or norleucine;
XAA 2 is either glycine or D-norleucine;
XAA 3 is valine or alanine;
Ava is 5-aminovaleric acid; and
Z 2 is an optionally present protecting group that, if present, is covalently joined to the C-terminal carboxy group;
or a pharmaceutically acceptable salt of said peptide;
wherein said peptide is optionally labeled with a detectable label selected from the group consisting of: luminescent, enzymatic and radioactive.
3. The peptide of claim 2 , wherein Z 2 is —NH 2 .
4. The peptide of claim 1 , wherein said peptide is either SEQ ID NO: 11, SEQ ID NO: 16, SEQ ID NO: 20, SEQ ID NO: 27, or a pharmaceutically acceptable salt thereof.
5. The peptide of claim 4 , wherein said peptide is either SEQ ID NO: 11, SEQ ID NO: 27 or a pharmaceutically acceptable salt thereof.
6. A method of inhibiting MCH-1R activity in a subject comprising the step of administering to said subject an effective amount of a peptide consisting of the structure:
wherein Gva is des-amino arginine;
XAA 1 is either methionine or norleucine;
XAA 2 is either or D-norleucine;
XAA 3 is valine or alanine;
Ava is 5-aminovaleric acid; and
Z 2 is an optionally present protecting group that, if present, is covalently joined to the C-terminal carboxy group;
or a pharmaceutically acceptable salt of said peptide.
7. The method of claim 6 , wherein Z 2 is —NH 2 .
8. The method of claim 6 , wherein said peptide is either SEQ ID NO: 11, SEQ ID NO: 16, SEQ ID NO: 20, SEQ ID NO: 27, or a pharmaceutically acceptable salt thereof.
9. The method of claim 6 , wherein said peptide is either SEQ ID NO: 11, SEQ ID NO: 27 or a pharmaceutically acceptable salt thereof.
10. A method of treating a subject to achieve a weight loss or to maintain weight comprising the step of administering to said subject an effective amount of a peptide consisting of the structure;
wherein Gva is des-amino arginine;
XAA 1 is either methionine or norleucine;
XAA 2 is either glycine or D-norleucine;
XAA 3 is valine or alanine;
Ava is 5-aminovaleric acid; and
Z 2 is an optionally present protecting group that, if present, is covalently joined to the C-terminal carboxy group;
or a pharmaceutically acceptable salt of said peptide.
11. The method of claim 10 , wherein said method causes a weight loss.
12. The method of claim 10 wherein Z 2 is —NH 2 .
13. The method of claim 10 , wherein said peptide is either SEQ ID NO: 11, SEQ ID NO: 16, SEQ ID NO: 20, SEQ ID NO: 27, or a pharmaceutically acceptable salt thereof.
14. The method of claim 10 , wherein said peptide is either SEQ ID NO: 11, SEQ ID NO: 27 or a pharmaceutically acceptable salt thereof.