Cargando…

Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products

[Image: see text] A thermodynamic approach to peptide macrocyclization inspired by the cyclization of non-ribosomal peptide aldehydes is presented. The method provides access to structurally diverse macrocycles by exploiting the reactivity of transient macrocyclic peptide imines toward inter- and in...

Descripción completa

Detalles Bibliográficos
Autores principales: Malins, Lara R., deGruyter, Justine N., Robbins, Kevin J., Scola, Paul M., Eastgate, Martin D., Ghadiri, M. Reza, Baran, Phil S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2017
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391502/
https://www.ncbi.nlm.nih.gov/pubmed/28326777
http://dx.doi.org/10.1021/jacs.7b01624
_version_ 1783229279500238848
author Malins, Lara R.
deGruyter, Justine N.
Robbins, Kevin J.
Scola, Paul M.
Eastgate, Martin D.
Ghadiri, M. Reza
Baran, Phil S.
author_facet Malins, Lara R.
deGruyter, Justine N.
Robbins, Kevin J.
Scola, Paul M.
Eastgate, Martin D.
Ghadiri, M. Reza
Baran, Phil S.
author_sort Malins, Lara R.
collection PubMed
description [Image: see text] A thermodynamic approach to peptide macrocyclization inspired by the cyclization of non-ribosomal peptide aldehydes is presented. The method provides access to structurally diverse macrocycles by exploiting the reactivity of transient macrocyclic peptide imines toward inter- and intramolecular nucleophiles. Reactions are performed in aqueous media, in the absence of side chain protecting groups, and are tolerant of all proteinogenic functional groups. Macrocyclic products bearing non-native and rigidifying structural motifs, isotopic labels, and a variety of bioorthogonal handles are prepared, along with analogues of four distinct natural products. Structural interrogation of the linear and macrocyclic peptides using variable-temperature NMR and circular dichroism suggests that preorganization of linear substrates is not a prerequisite for macrocyclization.
format Online
Article
Text
id pubmed-5391502
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-53915022017-04-15 Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products Malins, Lara R. deGruyter, Justine N. Robbins, Kevin J. Scola, Paul M. Eastgate, Martin D. Ghadiri, M. Reza Baran, Phil S. J Am Chem Soc [Image: see text] A thermodynamic approach to peptide macrocyclization inspired by the cyclization of non-ribosomal peptide aldehydes is presented. The method provides access to structurally diverse macrocycles by exploiting the reactivity of transient macrocyclic peptide imines toward inter- and intramolecular nucleophiles. Reactions are performed in aqueous media, in the absence of side chain protecting groups, and are tolerant of all proteinogenic functional groups. Macrocyclic products bearing non-native and rigidifying structural motifs, isotopic labels, and a variety of bioorthogonal handles are prepared, along with analogues of four distinct natural products. Structural interrogation of the linear and macrocyclic peptides using variable-temperature NMR and circular dichroism suggests that preorganization of linear substrates is not a prerequisite for macrocyclization. American Chemical Society 2017-03-22 2017-04-12 /pmc/articles/PMC5391502/ /pubmed/28326777 http://dx.doi.org/10.1021/jacs.7b01624 Text en Copyright © 2017 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Malins, Lara R.
deGruyter, Justine N.
Robbins, Kevin J.
Scola, Paul M.
Eastgate, Martin D.
Ghadiri, M. Reza
Baran, Phil S.
Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products
title Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products
title_full Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products
title_fullStr Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products
title_full_unstemmed Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products
title_short Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products
title_sort peptide macrocyclization inspired by non-ribosomal imine natural products
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391502/
https://www.ncbi.nlm.nih.gov/pubmed/28326777
http://dx.doi.org/10.1021/jacs.7b01624
work_keys_str_mv AT malinslarar peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts
AT degruyterjustinen peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts
AT robbinskevinj peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts
AT scolapaulm peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts
AT eastgatemartind peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts
AT ghadirimreza peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts
AT baranphils peptidemacrocyclizationinspiredbynonribosomaliminenaturalproducts