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Electrochemical Tryptophan-Selective Bioconjugation

preprint
submitted on 02.03.2019 and posted on 05.03.2019 by Eisho Toyama, Katsuya Maruyama, Tomoya Sugai, Mio Kondo, Shigeyuki Masaoka, Tsuyoshi Saitoh, Kounosuke Oisaki, Motomu Kanai

Bioconjugation reactions are a fundamental synthetic method for generating artificial peptides and proteins. Despite the potentially superior properties of bioconjugates at hydrophobic amino acid residues compared with those at hydrophilic amino acids, methods to target hydrophobic amino acids with moderate reactivity under mild and metal-free conditions are limited. Here we report the first electrochemically-promoted tryptophan (Trp)-selective bioconjugation of peptides and proteins in neutral aqueous media. The unique electrochemical cooperation of two radicals, keto-ABNO and 4-oxo-TEMPO, was critical to suppress both anodic overoxidation of the products and cross reactivity. Systematic cyclic voltammetry analysis suggested that these two radicals, containing similar redox potentials but contrasting steric demands, had distinct electrochemical roles (reactant and electrochemical mediator). This new protocol will be an important advance toward clean and scalable syntheses of chemically modified biologics.

Funding

JSPS KAKENHI JP17H06442 (Hybrid Catalysis)

JSPS KAKENHI JP17H01522

JSPS KAKENHI JP18K06545

JSPS KAKENHI JP18H04239 (Precisely Designed Cata-lysts with Customized Scaffolding)

Fugaku Trust for Medical Research

Astellas Foundation for Research on Metabolic Disorders

JSPS KAKENHI JP16H04125

JSPS KAKENHI JP17H06444 (Hybrid Catalysis)

JSPS KAKENHI JP15H05480

JSPS KAKENHI JP17K19185

History

Email Address of Submitting Author

oisaki@mol.f.u-tokyo.ac.jp

Institution

The University of Tokoyo

Country

Japan

ORCID For Submitting Author

0000-0002-0499-8168

Declaration of Conflict of Interest

none

Exports