Author/Authors :
Liang Z. Yan، نويسنده , , David Flora، نويسنده , , Patrick Edwards، نويسنده , , David L. Smiley، نويسنده , , Paul J. Emmerson، نويسنده , , Hansen M. Hsiung، نويسنده , , Robert Gadski، نويسنده , , JeAnne Hertel، نويسنده , , Mark L. Heiman، نويسنده , , Saba Husain، نويسنده , , Thomas P. O’Brien، نويسنده , , Steven D. Kahl، نويسنده , , Lianshan Zhang، نويسنده , , Richard D. DiMarchi، نويسنده , , John P. Mayer، نويسنده ,
Abstract :
Extensive structure–activity relationship studies utilizing a β-MSH-derived cyclic nonapeptide, Ac-Tyr-Arg-[Cys-Glu-His-d-Phe-Arg-Trp-Cys]-NH2 (3), led to identification of a series of novel MC-4R selective disulfide-constrained hexapeptide analogs including Ac-[hCys-His-d-Phe-Arg-Trp-Cys]-NH2 (12). The structural modifications associated with profound influence on MC-4R potency and selectivity were ring size, ring conformation, and the aromatic substitution of the d-Phe7. These cyclic peptide analogs provide novel and enhanced reagents for use in the elucidation of melanocortin-4 receptor-related physiology, and may additionally find application in the treatment of obesity and related metabolic disorders.
