Glycan-Mediated, Ligand-Controlled Click Chemistry for Drug-Target Identification

Henning Stöckmann; Violeta L Marin; Paul Nimmer; Corina M Balut; Donald J Davidson; Paul L Richardson; Anil Vasudevan

doi:10.1002/cbic.201500590

Glycan-Mediated, Ligand-Controlled Click Chemistry for Drug-Target Identification

Chembiochem. 2016 Jan;17(2):150-4. doi: 10.1002/cbic.201500590. Epub 2015 Dec 23.

Authors

Henning Stöckmann¹, Violeta L Marin², Paul Nimmer², Corina M Balut², Donald J Davidson², Paul L Richardson², Anil Vasudevan²

Affiliations

¹ Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA. [email protected].
² Discovery Chemistry and Technology, Oncology Discovery, Integrated Sciences and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.

PMID: 26574896
DOI: 10.1002/cbic.201500590

Abstract

Membrane-bound proteins are important pharmaceutical drug targets, yet few strategies exist for the identification of small-molecule-targeted membrane proteins in live-cell systems. By exploiting metabolic glycan engineering of cell membrane proteins, we have developed an in situ glycan-mediated ligand-controlled click ("GLiCo-Click") chemistry methodology that enables the attachment of small-molecule chemical probes to their receptor protein through glycans on live cells. In addition to enabling receptor enrichment from cell lysates, this strategy can be used to demonstrate target receptor engagement and enables the molecular characterization of receptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Antigens, Surface / chemistry
Chromatography, Liquid
Click Chemistry
Drug Delivery Systems*
Flow Cytometry
Ligands
Microscopy, Confocal
Molecular Sequence Data
Molecular Structure
Polysaccharides / chemistry*

Substances

Antigens, Surface
Ligands
Polysaccharides