Efficient Synthesis of Disulfide Bridge Containing Peptides: Melanin Concentrating Hormone (MCH) and Brain Natriuretic Peptide (BNP)

摘要

Melanin-concentrating hormone (MCH) DFDMLRC*MLGRVYRPC*WQV is an endogenous neuropeptide expressed in the hypothalamus. The mammalian MCH receptor is an attractive target for treatment of obesity and obesity-associated pathologies. Brain natriuretic peptide (BNP) SPKMVQGSGC*FGRKMDRISSSS-GLGC*KVLRRH is a well-known cardiac hormone, which has several pharmacological activities including diuretic-natriuretic, hypotensive and vasorelaxant actions. Both MCH and BNP are disulfide cyclic peptides. We report the rapid, practical, high-yield synthesis of full-length MCH [3], full-length BNP and derivatives of each, using solid-phase assembly of the linear precursor followed by optimized solution-phase disulfide macrocyclization. (C*...C*, indicates disulfide bridge).