Potent and selective MC-4 receptor agonists based on a novel disulfide scaffold

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• 作者：Liang Z. Yan ; David Flora ; Patrick Edwards ; David L. Smiley ; Paul J. Emmerson ; Hansen M. Hsiung ; Robert Gadski ; JeAnne Hertel ; Mark L. Heiman ; Saba Husain et al.
• 关键词：Melanocortin receptor agonist
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：15
• 期：20
• 页码：4611-4614
• 全文大小：118 K

文摘

Extensive structure–activity relationship studies utilizing a β-MSH-derived cyclic nonapeptide, Ac-Tyr-Arg-[Cys-Glu-His-class=""smCaps"">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-class=""smCaps"">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 class=""smCaps"">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.