O-GlcNAc transferase inhibitors: current tools and future challenges

TY - JOUR

T1 - O-GlcNAc transferase inhibitors

T2 - current tools and future challenges

AU - Trapannone, Riccardo

AU - Rafie, Karim

AU - Van Aalten, Daan M. F.

N1 - This work was supported by Wellcome Trust Senior Research Fellowship WT087590MA to DVA. RT is funded by a Wellcome Trust 4-year PhD studentship.

PY - 2016/2/15

Y1 - 2016/2/15

N2 - The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O-GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges.

AB - The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O-GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges.

KW - Inhibitor

KW - O-linked N-acetylglucosamine

KW - O-linked N-acetylglucosamine (O-GlcNAc)

UR - https://www.scopus.com/pages/publications/84957927004

U2 - 10.1042/BST20150189

DO - 10.1042/BST20150189

M3 - Article

C2 - 26862193

AN - SCOPUS:84957927004

SN - 0300-5127

VL - 44

SP - 88

EP - 93

JO - Biochemical Society Transactions

JF - Biochemical Society Transactions

IS - 1

ER -