Author:
Weng Yue,Su Chun-Jen,Jiang Haoyang,Chiang Chien-Wei
Abstract
AbstractSite-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation. However, the covalent bioconjugation of native phenylalanine is one of the most challenging problems in protein modification. Herein, an approach to protein modification is described that relies on a photoredox method for the site-selective bioconjugation of phenylalanine. This methodology has been validated on peptides as well as protein insulin using a straightforward and mild condition. In addition, based on characterization by near-UV CD spectroscopy and small angle X-ray scattering (SAXS), this pyrazole labeling approach permitted the insulin hexamer to completely dissociate into the monomeric form, thus making it a potential candidate for use as rapid-acting insulin for the treatment of diabetes.
Funder
National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology
Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Hubei University
National Science and Technology Council, Taiwan
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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