Novel Melanocortin Receptor Templates, Peptides, and Use Thereof

Abstract

The present invention relates to novel chimeric peptides and templates containing a combination of antagonist and agonist endogenous ligand residues. In particular, the present invention relates to novel chimeric peptides and templates thereof based upon melanocortin agonist peptides and agouti related protein (AGRP). The present invention provides multifunctional chimeric peptides having specific bioactivity at melanocortin receptors and their use as drugs to treat various diseases and conditions.

1 . A method for treating in a patient a condition modulated by melanocortin receptors, the method comprising administering to the patient a composition comprising a peptide that is biologically active at melanocortin receptors comprising an AGRP(109-118) template and melanocortin agonist-based bioactive determinant sequences which have been substituted for the analogous template sequences, and an acceptable carrier or diluent, wherein
 a) the melanocortin agonist-based bioactive determinant sequence is selected from the group consisting of:
 i) Trp-Arg-Phe; 
 ii) Trp-Arg-DPhe; 
 iii) Phe-Arg-Tip; 
 iv) DPhe-Arg-Trp; 
 v) His-Phe-Arg-Trp; and 
 vi) His-DPhe-Arg-Trp. 
   
     
     
         2 . The method according to  claim 1 , wherein the peptide is of any SEQ ID Nos. 4-7, 9, and 10. 
     
     
         3 . The method according to  claim 1 , wherein the peptide is administered via oral route; injection or infusion by intravenous, intraperitoneal, intracerebral (intraparenchymal), intracerebroventricular, intramuscular, intraocular, intraarterial, or intralesional routes; intranasal route; sustained release systems; or implantation device. 
     
     
         4 . The method according to  claim 3 , wherein the composition is administered orally.