Peptide Model of the Mutant Proinsulin Syndrome. I. Design and Clinical Correlation.

ABSTRACT: The mutant proinsulin syndrome is a monogenic cause of diabetes mellitus due to toxic misfolding of insulin's biosynthetic precursor. Also designated mutant INS-gene induced diabetes of the young (MIDY), this syndrome defines molecular determinants of foldability in the endoplasmic reticulum (ER) of β-cells. Here, we describe a peptide model of a key proinsulin folding intermediate and variants containing representative clinical mutations; the latter perturb invariant core sites in native proinsulin (Leu^B15→Pro, Leu^A16→Pro, and Phe^B24→Ser). The studies exploited a 49-residue single-chain synthetic precursor (designated DesDi), previously shown to optimize in vitro efficiency of disulfide pairing. Parent and variant peptides contain a single di

SUBMITTER: Dhayalan B 

PROVIDER: S-EPMC8922534 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature