Synthesis and evaluation of bivalent NDP-alpha-MSH(7) peptide ligands for binding to the human melanocortin receptor 4 (hMC4R).

ABSTRACT: We demonstrate the potential utility of multivalent ligands as targeting agents for cancer imaging or therapy by determining the binding of homobivalent ligands to their corresponding receptors. This manuscript details the synthesis and evaluation of a series of bivalent ligands containing two copies of the truncated heptapeptide version of [Nle4-D-Phe7]-alpha-melanocyte stimulating hormone (NDP-alpha-MSH), referred to as MSH(7). These were connected with various semirigid linkers containing Pro-Gly repeats, with or without flexible poly(ethylene glycol) (PEGO) moieties at their termini. Modeling data suggest a distance of 20-50 A between the ligand binding sites of two adjacent G-protein coupled receptors, GPCRs. These bivalent ligands were observed to bind with higher affinity compared t

SUBMITTER: Handl HL 

PROVIDER: S-EPMC3538036 | biostudies-literature | 2007 Jul-Aug

REPOSITORIES: biostudies-literature