Genetic Incorporation of a Reactive Isothiocyanate Group into Proteins

Xuan, Weimin; Li, Jack; Luo, Xiaozhou; Schultz, Peter G.

doi:10.1002/ange.201604891

Title: Genetic Incorporation of a Reactive Isothiocyanate Group into Proteins

Journal Article · 15 July 2016 · Angewandte Chemie

DOI: https://doi.org/10.1002/ange.201604891 · OSTI ID:1401452

Xuan, Weimin ^[1]; Li, Jack ^[1]; Luo, Xiaozhou ^[1]; Schultz, Peter G. ^[1]

Department of Chemistry The Scripps Research Institute 10550 N. Torrey Pines Road La Jolla CA 92037 USA

Abstract Methods for the site‐specific modification of proteins are useful for introducing biological probes into proteins and engineering proteins with novel activities. Herein, we genetically encode a novel noncanonical amino acid (ncAA) that contains an aryl isothiocyanate group which can form stable thiourea crosslinks with amines under mild conditions. We show that this ncAA (pNCSF) allows the selective conjugation of proteins to amine‐containing molecular probes through formation of a thiourea bridge. pNCSF was also used to replace a native salt bridge in myoglobin with an intramolecular crosslink to a proximal Lys residue, leading to increased thermal stability. Finally, we show that pNCSF can form stable intermolecular crosslinks between two interacting proteins.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: SC0011787

OSTI ID:: 1401452

Journal Information:: Angewandte Chemie, Journal Name: Angewandte Chemie Journal Issue: 34 Vol. 128; ISSN 0044-8249

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: Germany

Language:: English

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