Issue 8, 2015

Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation

Abstract

The α-ketoacid–hydroxylamine (KAHA) ligation with 5-oxaproline enables the direct cyclization of peptides upon cleavage from a solid support, without coupling reagents, protecting groups, or purification of the linear precursors. This Fmoc SPPS-based method was applied to the synthesis of a library of 24 homoserine-containing cyclic peptides and was compared side-by-side with the synthesis of the same products using a standard method for cyclizing side-chain protected substrates. A detailed mechanistic study including 2H and 18O labeling experiments and the characterization of reaction intermediates by NMR and mass spectrometry is reported.

Graphical abstract: Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Maijs 2015
Accepted
05 Jūn. 2015
First published
10 Jūn. 2015
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2015,6, 4889-4896

Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation

F. Rohrbacher, G. Deniau, A. Luther and J. W. Bode, Chem. Sci., 2015, 6, 4889 DOI: 10.1039/C5SC01774B

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