Binding conformation and determinants of a single-chain peptide antagonist at the relaxin-3 receptor RXFP3.

ABSTRACT: The neuropeptide relaxin-3 and its receptor relaxin family peptide receptor-3 (RXFP3) play key roles in modulating behavior such as memory and learning, food intake, and reward seeking. A linear relaxin-3 antagonist (R3 B1-22R) based on a modified and truncated relaxin-3 B-chain was recently developed. R3 B1-22R is unstructured in solution; thus, the binding conformation and determinants of receptor binding are unclear. Here, we have designed, chemically synthesized, and pharmacologically characterized more than 60 analogues of R3 B1-22R to develop an extensive understanding of its structure-activity relationships. We show that the key driver for affinity is the nonnative C-terminal Arg²³ Additional contributors to binding include amino acid residues that are important also for

SUBMITTER: Haugaard-Kedstrom LM 

PROVIDER: S-EPMC6187623 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature