Journal article
Binding conformation and determinants of a single-chain peptide antagonist at the relaxin-3 receptor RXFP3
LM Haugaard-Kedström, HS Lee, MV Jones, A Song, V Rathod, MA Hossain, RAD Bathgate, KJ Rosengren
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2018
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 pharmacologi-cally 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. ..
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Awarded by Australian Research Council
Funding Acknowledgements
[ "This work was supported by the National Health and Medical Research Council (NHMRC), Australia, through Project Grants 1063425 and 1066369 (to R. A. D. B. and K. J. R.). Research at the Florey was supported by the Victorian Government Operational Infrastructure Support Program. L. M. H. K., K. J. R., and R. A. D. B. are inventors on Australian Patent 2010904046 and United States patent application 13/821726, Modified Relaxin B Chain Peptides.", "Supported by an Australian Research Council Future Fellowship." ]