The C-terminus of the B-chain of human insulin-like peptide 5 is critical for cognate RXFP4 receptor activity

NA Patil; RAD Bathgate; M Kocan; SY Ang; J Tailhades; F Separovic; R Summers; J Grosse; RA Hughes; JD Wade; MA Hossain

Journal article

The C-terminus of the B-chain of human insulin-like peptide 5 is critical for cognate RXFP4 receptor activity

NA Patil, RAD Bathgate, M Kocan, SY Ang, J Tailhades, F Separovic, R Summers, J Grosse, RA Hughes, JD Wade, MA Hossain

Amino Acids | SPRINGER WIEN | Published : 2016

DOI: 10.1007/s00726-015-2144-5

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Abstract

Insulin-like peptide 5 (INSL5) is an orexigenic peptide hormone belonging to the relaxin family of peptides. It is expressed primarily in the L-cells of the colon and has a postulated key role in regulating food intake. Its G protein-coupled receptor, RXFP4, is a potential drug target for treating obesity and anorexia. We studied the effect of modification of the C-terminus of the A and B-chains of human INSL5 on RXFP4 binding and activation. Three variants of human INSL5 were prepared using solid phase peptide synthesis and subsequent sequential regioselective disulfide bond formation. The peptides were synthesized as C-terminal acids (both A- and B-chains with free C-termini, i.e., the nat..

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University of Melbourne Researchers

Ross Bathgate Author

Frances Separovic Author

Akhter Hossain Author

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Awarded by Australian Research Council

Funding Acknowledgements

This research was partly funded by NHMRC (Australia) project grants ( 1023321, 1065481, 1023078) to M. A. H, R. A. D. B and J. D. W and ARC linkage grant (LP120100654) to R. A. H. We are grateful to Tania Ferraro and Sharon Layfield for assistance with biochemical assays. During these studies, M. A. H. was the recipient of Florey Foundation Fellowships. R. A. D. B. is an NHMRC Senior Research Fellow, and J. D. W. is an NHMRC Principal Research Fellow. Studies at the FINMH were supported by the Victorian Government's Operational Infrastructure Support Program.