Disulfide bridges contribute to the definition and rigidity of polypeptides, but they are inherently unstable in reducing environments and in the presence of isomerases and nucleophiles. Strategies to address these...
Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next‐generation drugs. Separate synthesis of multiple peptide fragments and tedious chain‐to‐chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre‐made diaminodiacid bridge at A‐B chain terminal disulfide can be easily and rapidly synthesized by a single‐shot automated solid‐phase synthesis and expedient one‐step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies.
Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next‐generation drugs. Separate synthesis of multiple peptide fragments and tedious chain‐to‐chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre‐made diaminodiacid bridge at A‐B chain terminal disulfide can be easily and rapidly synthesized by a single‐shot automated solid‐phase synthesis and expedient one‐step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies.
The replacement of disulfide bridges with metabolically stable isosteres is a promising strategy to improve the stability of disulfide-rich polypeptides towards reducing agents and isomerases. Diaminodiacid-based strategy is one of...
The replacement of disulfide bonds with metabolically stable isosteres by a diaminodiacid strategy has been demonstrated as an effective and flexible method to improve the stability of disulfide-rich peptides. In...
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