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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2017
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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 |
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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 |
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