A General Approach Towards Triazole-Linked Adenosine Diphosphate Ribosylated Peptides and Proteins

Author(s):
Liu, Q.; Kistemaker, H.A.V.; Bhogaraju, S.; Dikic, I.; Overkleeft, H.S. (0000-0001-6992-4760); Marel, G.A. van der (0000-0001-8917-3458); Ovaa, H.; Heden van Noort, G.J. van der; Filippov, D.V. (0000-0002-6978-7425)
Published
2018
Publication type
Article / Letter to editor

Abstract

Current methods to prepare adenosine diphosphate ribosylated (ADPr) peptides are not generally applicable due to the labile nature of this post-translational modification and its incompatibility with strong acidic conditions used in standard solid-phase peptide synthesis. A general strategy is presented to prepare ADPr peptide analogues based on a copper-catalyzed click reaction between an azide-modified peptide and an alkyne-modified ADPr counterpart. The scope of this approach was expanded to proteins by preparing two ubiquitin ADPr analogues carrying the biological relevant α-glycosidic linkage. Biochemical validation using Legionella effector enzyme SdeA shows that clicked ubiquitin ADPr is well-tolerated and highlights the potential of this strategy to prepare ADPr proteins.

Date issued
2018-01-08
Language
English
Is part of
Angewandte Chemie (International ed. in English) (2018), Vol. 57, no. 6, p. 1659-1662
hdl
1887/67302
doi
10.1002/anie.201710527