Rapid Photolysis-Mediated Folding of Disulfide-Rich Peptides |
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Authors: | Dr. Nitin A. Patil Dr. John A. Karas Prof. Dr. John D. Wade Dr. Mohammed Akhter Hossain Dr. Julien Tailhades |
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Affiliation: | 1. The Monash Biomedicine Discovery Institute, 15 Innovation Walk, Clayton, VIC 3800 Australia;2. Department of Pharmacology and Therapeutics, The University of Melbourne, Victoria, 3010 Australia |
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Abstract: | Structure–activity relationship studies are a highly time-consuming aspect of peptide-based drug development, particularly in the assembly of disulfide-rich peptides, which often requires multiple synthetic steps and purifications. Therefore, it is vital to develop rapid and efficient chemical methods to readily access the desired peptides. We have developed a photolysis-mediated “one-pot” strategy for regioselective disulfide bond formation. The new pairing system utilises two ortho-nitroveratryl protected cysteines to generate two disulfide bridges in less than one hour in good yield. This strategy was applied to the synthesis of complex disulfide-rich peptides such as Rho-conotoxin ρ-TIA and native human insulin. |
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Keywords: | disulfides peptides photolysis protein engineering protein folding structure–activity relationships |
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