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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins

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Author(s):
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Weller, Caroline E. ; Dhall, Abhinav ; Ding, Feizhi ; Linares, Edlaine ; Whedon, Samuel D. ; Senger, Nicholas A. ; Tyson, Elizabeth L. ; Bagert, John D. ; Li, Xiaosong ; Augusto, Ohara ; Chatterjee, Champak
Total Authors: 11
Document type: Journal article
Source: NATURE COMMUNICATIONS; v. 7, SEP 29 2016.
Web of Science Citations: 21
Abstract

Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N-O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N-O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins. (AU)

FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC