Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation

[Image: see text] In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocycli...

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Autores principales: Streefkerk, Dieuwertje E., Schmidt, Marcel, Ippel, Johannes H., Hackeng, Tilman M., Nuijens, Timo, Timmerman, Peter, van Maarseveen, Jan H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456872/
https://www.ncbi.nlm.nih.gov/pubmed/30912446
http://dx.doi.org/10.1021/acs.orglett.9b00378
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author Streefkerk, Dieuwertje E.
Schmidt, Marcel
Ippel, Johannes H.
Hackeng, Tilman M.
Nuijens, Timo
Timmerman, Peter
van Maarseveen, Jan H.
author_facet Streefkerk, Dieuwertje E.
Schmidt, Marcel
Ippel, Johannes H.
Hackeng, Tilman M.
Nuijens, Timo
Timmerman, Peter
van Maarseveen, Jan H.
author_sort Streefkerk, Dieuwertje E.
collection PubMed
description [Image: see text] In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocyclization, CLIPS alkylation, and oxime ligation to prepare tetracyclic peptides. Five new small molecular scaffolds and differently sized model peptides featuring noncanonical amino acids were synthesized. Enzymatic macrocyclization, followed by one-pot scaffold-assisted cyclizations, yielded 21 tetracyclic peptides in a facile and robust manner.
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spelling pubmed-64568722019-04-11 Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation Streefkerk, Dieuwertje E. Schmidt, Marcel Ippel, Johannes H. Hackeng, Tilman M. Nuijens, Timo Timmerman, Peter van Maarseveen, Jan H. Org Lett [Image: see text] In Nature, multicyclic peptides constitute a versatile molecule class with various biological functions. For their pharmaceutical exploitation, chemical methodologies that enable selective consecutive macrocyclizations are required. We disclose a combination of enzymatic macrocyclization, CLIPS alkylation, and oxime ligation to prepare tetracyclic peptides. Five new small molecular scaffolds and differently sized model peptides featuring noncanonical amino acids were synthesized. Enzymatic macrocyclization, followed by one-pot scaffold-assisted cyclizations, yielded 21 tetracyclic peptides in a facile and robust manner. American Chemical Society 2019-03-26 2019-04-05 /pmc/articles/PMC6456872/ /pubmed/30912446 http://dx.doi.org/10.1021/acs.orglett.9b00378 Text en Copyright © 2019 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.
spellingShingle Streefkerk, Dieuwertje E.
Schmidt, Marcel
Ippel, Johannes H.
Hackeng, Tilman M.
Nuijens, Timo
Timmerman, Peter
van Maarseveen, Jan H.
Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
title Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
title_full Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
title_fullStr Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
title_full_unstemmed Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
title_short Synthesis of Constrained Tetracyclic Peptides by Consecutive CEPS, CLIPS, and Oxime Ligation
title_sort synthesis of constrained tetracyclic peptides by consecutive ceps, clips, and oxime ligation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456872/
https://www.ncbi.nlm.nih.gov/pubmed/30912446
http://dx.doi.org/10.1021/acs.orglett.9b00378
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