RESUMEN
Extensive two-dimensional NMR analysis was employed to characterize the structural identity of the macrocyclic peptide lactam and the imide analog, a major side reaction product when allyl ester was used to protect the side chain of aspartic acid. A straightforward protocol modification was developed to minimize aspartimide formation during the synthesis of cyclic peptides.
Asunto(s)
Ácido Aspártico/análogos & derivados , Péptidos Cíclicos/síntesis química , Técnicas Químicas Combinatorias , Lactamas , Espectroscopía de Resonancia Magnética , Estructura Molecular , Péptidos Cíclicos/aislamiento & purificación , Control de CalidadRESUMEN
Extensive structure-activity relationship studies utilizing a beta-MSH-derived cyclic nonapeptide, Ac-Tyr-Arg-[Cys-Glu-His-D-Phe-Arg-Trp-Cys]-NH(2) (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]-NH(2) (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.