G PROTEIN-COUPLED PEPTIDE RECEPTORS: STATE OF THE ART AND INNOVATIVE THERAPEUTIC CONCEPTS
Prof. Annette G. Beck-Sickinger （Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Germany）
日時：令和5 年11 月7 日（火）10:45～11:45
場所：中百舌鳥キャンパス A13 棟 323 号室（講義室B）
Peptides hormones play an important role in the regulation of manifold activi-ties in the body. Many of them transmit their activity through G protein-coupled receptors (GPCR), which are among the most promising drug targets nowadays. However, in addition to their direct activity, indirect mechanisms have been shown to play an important role, e. g. as drug shuttles in tumour targeting. Accordingly, in addition to ligand binding, internalization has to be addressed and to be studied, including arrestin recruitment. The neuropeptide Y/pancreatic polypeptide family contains 36 amino acid peptides, which bind to four different so-called Y-receptors in human. By a combination of X-ray anal-ysis, cryo-EM, NMR, molecular modelling and crosslinking combined with mass spectrometry, we have recently identified the distinct binding modes of NPY peptides to their Y-receptors. Neuropeptide Y receptors have been shown to play a relevant role in the regulation of food intake. Furthermore, they partici-pate in adipogenesis and some of them are overexpressed in tumours. By knowing the receptor bound structure, specific ligands as well as peptide-drug conjugates have been designed to selectively address Y receptors in different tissues including allo-steric modulators.