LATE-STAGE FUNCTIONALIZATION OF PEPTIDES AND CYCLOPEPTIDES USING ORGANOZINC REAGENTS

We have reported a new late-stage functionalization of small peptides and cyclopeptides using readily prepared iodotyrosine or iodophenylalanine containing peptides and performing Negishi cross-couplings with aryl-, heteroaryl- and alkyl-zinc pivalates or halides. In-silico and in-vitro determinations of membrane permeability data of the modified cyclopeptides showed that in most cases, the solubility was improved while the cell-membrane permeability was maintained by the introduction of polar pyridyl units.