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

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...

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Autores principales: Rohrbacher, Florian, Deniau, Gildas, Luther, Anatol, Bode, Jeffrey W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664356/
https://www.ncbi.nlm.nih.gov/pubmed/29142720
http://dx.doi.org/10.1039/c5sc01774b
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author Rohrbacher, Florian
Deniau, Gildas
Luther, Anatol
Bode, Jeffrey W.
author_facet Rohrbacher, Florian
Deniau, Gildas
Luther, Anatol
Bode, Jeffrey W.
author_sort Rohrbacher, Florian
collection PubMed
description 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 (2)H and (18)O labeling experiments and the characterization of reaction intermediates by NMR and mass spectrometry is reported.
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spelling pubmed-56643562017-11-15 Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation Rohrbacher, Florian Deniau, Gildas Luther, Anatol Bode, Jeffrey W. Chem Sci Chemistry 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 (2)H and (18)O labeling experiments and the characterization of reaction intermediates by NMR and mass spectrometry is reported. Royal Society of Chemistry 2015-08-01 2015-06-10 /pmc/articles/PMC5664356/ /pubmed/29142720 http://dx.doi.org/10.1039/c5sc01774b Text en This journal is © The Royal Society of Chemistry 2015 http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Chemistry
Rohrbacher, Florian
Deniau, Gildas
Luther, Anatol
Bode, Jeffrey W.
Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation
title Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation
title_full Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation
title_fullStr Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation
title_full_unstemmed Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation
title_short Spontaneous head-to-tail cyclization of unprotected linear peptides with the KAHA ligation
title_sort spontaneous head-to-tail cyclization of unprotected linear peptides with the kaha ligation
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664356/
https://www.ncbi.nlm.nih.gov/pubmed/29142720
http://dx.doi.org/10.1039/c5sc01774b
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