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 5 2015
Accepted
05 6 2015
First published
10 6 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

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