Photoredox C–H functionalization leads the site-selective phenylalanine bioconjugation

Site-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...

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Bibliographic Details
Published in:Scientific reports 2022-11, Vol.12 (1), p.18994-18994, Article 18994
Main Authors: Weng, Yue, Su, Chun-Jen, Jiang, Haoyang, Chiang, Chien-Wei
Format: Article
Language:English
Subjects:
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Amino acids
Biopharmaceuticals
Catalysis
Chemistry
Decomposition
Diabetes
Diabetes mellitus
Humanities and Social Sciences
Insulin
Insulin - chemistry
multidisciplinary
Oxidation
Peptides
Peptides - chemistry
Phenylalanine
Phenylalanine - chemistry
Proteins
Proteins - chemistry
Pyrazoles
Scattering, Small Angle
Science
Science (multidisciplinary)
Spectroscopy
X-Ray Diffraction
X-ray scattering
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Summary:Site-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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-23481-6