Structure-Activity Relationship Study of Tachykinin Peptides for the Development of Novel NK3 Receptor Agonists

摘要

Pulsatile release of gonadotropin-releasing hormone (GnRH) is prerequisite for reproductive success in mammals. Recently, it was suggested that neurokinin B (NKB), an endogenous ligand for neurokinin-3 receptor (NK3R), plays a pivotal role in the central control of pulsatile GnRH secretion [1]. Thus, the NKB receptor(s) could be a pharmaceutical target to regulate pulsatile GnRH secretion. Although naturally occurring tachykinin peptides could provide appropriate lead peptides, most of them bind to all tachykinin receptors [neurokinin-1 receptor (NK1R), neurokinin-2 receptor (NK2R) and NK3R] with low selectivity. In order to identify the essential structural requirements for selective NK3R agonists, we carried out structure-activity relationship (SAR) study of [MePhe~7]-NKB and other tachykinin peptides [2].