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Palladium-Protein Oxidative Addition Complexes by Amine-Selective Acylation.

ABSTRACT: Palladium oxidative addition complexes (OACs) are traditionally accessed by treating an aryl halide-containing substrate with a palladium(0) source. Here, a new strategy to selectively prepare stable OACs from amino groups on native proteins is presented. The approach relies on an amine-selective acylation reaction that occurs without modification of a preformed palladium(II)-aryl group. Once transferred onto a protein substrate, the palladium(II)-aryl group facilitates conjugation by undergoing reaction with a second, cysteine-containing protein. This operationally simple method is applicable to native, nonengineered enzymes as well as antibodies and is carried out in an aqueous setting and open to air. The resulting Pd-protein OACs are stable, storable reagents that retain biological activity and can be used to achieve protein-protein cross-coupling at nanomolar concentrations within hours.

SUBMITTER: Dhanjee HH

PROVIDER: S-EPMC8048385 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Palladium-Protein Oxidative Addition Complexes by Amine-Selective Acylation.

Dhanjee Heemal H HH Buslov Ivan I Windsor Ian W IW Raines Ronald T RT Pentelute Bradley L BL Buchwald Stephen L SL

Journal of the American Chemical Society 20201215 51

Palladium oxidative addition complexes (OACs) are traditionally accessed by treating an aryl halide-containing substrate with a palladium(0) source. Here, a new strategy to selectively prepare stable OACs from amino groups on native proteins is presented. The approach relies on an amine-selective acylation reaction that occurs without modification of a preformed palladium(II)-aryl group. Once transferred onto a protein substrate, the palladium(II)-aryl group facilitates conjugation by undergoing ...[more]

PMID: 33319995

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