Efficient moderate scale synthesis of melanin concentrating hormone (MCH) for in vivo studies

摘要

First identified in chum salmon, the cyclic nonadecapeptide melanin-concentrating hormone (MCH) is produced in the hypothalamus of all mammals and possesses a single disulfide bridge (Fig. 1). MCH knockout mice are hypophagic and lean with increased metabolic rates, whereas animals over-expressing MCH gain excess weight on both standard and high-fat diets. In addition MCH stimulates feeding when injected into the lateral ventricle of rats. Because MCH has been shown to play such a major role in the regulation of food intake and energy metabolism in mammals MCH antagonism is an attractive target for therapeutic intervention to treat obesity. Ongoing efforts to identify orally active small molecule agents targeting the MCH pathway for the treatment of obesity require significant quantities of highly purified MCH, and to meet this need we developed the practical, gram-scale synthesis of MCH described here.