Premium
Late‐Stage Functionalization of Peptides and Cyclopeptides Using Organozinc Reagents
Author(s) -
Leroux Marcel,
Vorherr Thomas,
Lewis Ian,
Schaefer Michael,
Koch Guido,
Karaghiosoff Konstantin,
Knochel Paul
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201902454
Subject(s) - surface modification , combinatorial chemistry , chemistry , reagent , negishi coupling , cell permeability , membrane permeability , membrane , aryl , in silico , organic chemistry , biochemistry , alkyl , gene
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.