Development of a first-in-class O-GlcNAc transferase (OGT) inhibitor

National Center For Advancing Translational Sciences

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Abstract

Chemical Technology researchers develop small molecule and screening approaches that other scientists can use to pursue innovations in therapeutic development. O-GlcNAc transferase (OGT) is an essential enzyme that catalyzes the attachment of O-GlcNAc residues to nuclear and cytoplasmic proteins including kinases, transcription factors, histones and many other proteins which, in turn, regulate numerous cellular processes. O-GlcNAcylation is still not well understood, and small molecule inhibitors of OGT will be a key tool for the dissecting of this important enzymes function in the cell. Working with the Walker lab (Harvard), we have developed a novel small molecule OGT inhibitor and validated its activity in several different mammalian cell lines without affecting synthesis of cell surface N- or O-linked glycans. We are continuing to optimize this agent and are pursuing numerous collaborations using this probe of OGT biology to delineate its role in multiple cell lines and disease settings.