Synthesis and Characterization of the R27S Genetic Variant of Insulin-like Peptide 5.
Alexander N ZaykovVasily M GelfanovFa LiuRichard D DiMarchiPublished in: ChemMedChem (2018)
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.
Keyphrases
- high efficiency
- type diabetes
- endothelial cells
- genome wide
- primary care
- healthcare
- glycemic control
- dna methylation
- heart rate
- gene expression
- metabolic syndrome
- quality improvement
- molecularly imprinted
- climate change
- blood pressure
- high resolution
- anti inflammatory
- binding protein
- adipose tissue
- human health
- mass spectrometry
- pluripotent stem cells