High-Yield Synthesis of Human Insulin-Like Peptide 5 Employing a Nonconventional Strategy

A simplified route to synthesis of INSL5 is reported, where the elimination of intermediate purification steps and nonconventional disulfide pairing results in final yields that are an order of magnitude higher than in previously reported stepwise syntheses. The intramolecular disulfide of A-chain w...

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Bibliographic Details
Published in:Organic letters 2018-06, Vol.20 (12), p.3695-3699
Main Authors: Zaykov, Alexander N, Gelfanov, Vasily M, Liu, Fa, DiMarchi, Richard D
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Disulfides
Humans
Insulin - chemical synthesis
Molecular Structure
Peptides
Proteins - chemical synthesis
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Summary:A simplified route to synthesis of INSL5 is reported, where the elimination of intermediate purification steps and nonconventional disulfide pairing results in final yields that are an order of magnitude higher than in previously reported stepwise syntheses. The intramolecular disulfide of A-chain was produced by a thiol displacement of StBu-protected cysteine, and was followed by an A-B chain disulfide formation in dimethylsulfoxide (DMSO). The final disulfide was formed by deprotection of StBu-cysteines in hydrofluoric acid (HF) at room temperature, which is a historical approach infrequently employed today, followed by oxidation using 2,2-dithiobis­(5-nitropyridine) (DTNP) in acidic aqueous buffer. Throughout the synthesis, an isoacyl surrogate to a midsequence native amide bond was utilized to enhance solubility of the intermediate compounds.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.8b01501