Synthesis and biological activity of novel peptide mimetics as melanocortin receptor agonists.
A series of novel peptidomimetic analogs was prepared containing cyclohexyl, phenyl, or heterocyclic groups to ostensibly orient the guanidine or mimic of an arginine in a putative melanocortin receptor ligand pharmacophore. Some binding affinity at the melanocortin receptors MC(3) and MC(4) was noted. In silico docking also indicated that the relative positions of the hydrogen-bonding sites and hydrophobic regions of the compounds are reasonably well matched to the receptor-binding site. This may present a lead entry into a selective series of MC(4)R agonists.
Liu
Xue-Wei
XW
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore. xuewei@ntu.edu.sg
Ma
Jimei
J
Colson
Anny-Odile
AO
Doersen
Doreen Cross
DC
Ebetino
Frank H
FH
D001120:Arginine / Q000737:chemistry; D006146:Guanidines / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D018716:Molecular Mimicry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D044104:Receptor, Melanocortin, Type 3 / Q000819:agonists*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D006146:Guanidines; D010455:Peptides; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D014230:Triazoles; D001120:Arginine