Issue 34, 2018

Native chemical ligation at methionine bioisostere norleucine allows for N-terminal chemical protein ligation

Abstract

The development of γ-thionorleucine (ThioNle) as a handle for native chemical ligation–desulfurization is reported here. ThioNle is a new addition to the expanding thiolated amino acid toolbox and serves as a methionine substitute in NCL with the advantage that it lacks the undesirable oxidation-prone thioether moiety. Its usefulness for N-terminal ubiquitination is demonstrated by efficient preparation of fully synthetic linear diubiquitin with preserved protein folding compared to the expressed material. Interestingly, gel-based deubiquitinating assays revealed that the methionine to norleucine substitution did affect diubiquitin cleavage, which may indicate a more profound role for methionine in the interaction between ubiquitin and the deubiquitinating enzymes than has been known so far.

Graphical abstract: Native chemical ligation at methionine bioisostere norleucine allows for N-terminal chemical protein ligation

Supplementary files

Article information

Article type
Paper
Submitted
10 Jul 2018
Accepted
09 Aug 2018
First published
09 Aug 2018
This article is Open Access
Creative Commons BY-NC license

Org. Biomol. Chem., 2018,16, 6306-6315

Native chemical ligation at methionine bioisostere norleucine allows for N-terminal chemical protein ligation

B. Xin, B. D. M. van Tol, H. Ovaa and P. P. Geurink, Org. Biomol. Chem., 2018, 16, 6306 DOI: 10.1039/C8OB01627E

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements