Synthesis and Characterization of the R27S Genetic Variant of Insulin-like Peptide 5

ChemMedChem
Alexander N ZaykovRichard D DiMarchi

Abstract

We report the synthesis and in vitro bioactivity assessment for an insulin-like peptide 5 (INSL5) analogue that was recently discovered as a genetic mutation in an Amish population. The mutation was associated with improved metabolic status, and receptor-based antagonism was proposed as a potential mechanism for the altered phenotype. We determined the specific peptide analogue to be fully potent and of maximal efficacy at the human relaxin family peptide receptor 4 (RXFP4), suggesting an alternative basis for the observed effect. In preparation of this synthetically challenging hormone, we have introduced several improvements such as implementation of isoacyl chemistry for high-efficiency preparation of INSL5 B-chain and selective intramolecular A6-11 disulfide formation as a first step in sequential disulfide assembly.

References

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Citations

May 31, 2019·Chembiochem : a European Journal of Chemical Biology·Melrose Mailig, Fa Liu
Dec 31, 2019·Chembiochem : a European Journal of Chemical Biology·Rongjun HeFa Liu
Mar 11, 2021·Chemical Reviews·John A KarasMohammed Akhter Hossain
Jun 7, 2018·Organic Letters·Alexander N ZaykovRichard D DiMarchi

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