Late‐Stage Functionalization of Peptides and Cyclopeptides Using Organozinc Reagents

We report a new late‐stage functionalization of small peptides and cyclopeptides relying on the Negishi cross‐coupling of readily prepared iodotyrosine‐ or iodophenylalanine‐containing peptides with aryl‐, heteroaryl‐, and alkylzinc pivalates or halides. In silico and in vitro determinations of memb...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2019-06, Vol.58 (24), p.8231-8234
Main Authors: Leroux, Marcel, Vorherr, Thomas, Lewis, Ian, Schaefer, Michael, Koch, Guido, Karaghiosoff, Konstantin, Knochel, Paul
Format: Article
Language:English
Subjects:
Aromatic compounds
cross-coupling
cyclopeptides
Halides
Membrane permeability
organozinc
Parameter modification
Peptides
Permeability
Reagents
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Summary:We report a new late‐stage functionalization of small peptides and cyclopeptides relying on the Negishi cross‐coupling of readily prepared iodotyrosine‐ or iodophenylalanine‐containing peptides with aryl‐, heteroaryl‐, and alkylzinc pivalates or halides. In silico and in vitro determinations of membrane permeability parameters of the modified cyclopeptides showed that in most cases, the solubility was improved by the introduction of polar pyridyl units while the cell‐membrane permeability was maintained. Just in time: A late‐stage functionalization of small peptides and cyclopeptides relies on the Negishi cross‐coupling of readily prepared iodotyrosine‐ or iodophenylalanine‐containing peptides with aryl‐, heteroaryl‐ and alkylzinc pivalates or halides. In most cases, the solubility was improved by the introduction of polar pyridyl units, while the cell‐membrane permeability was maintained.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201902454