Substrate and product analogues as human O-GlcNAc transferase inhibitors.
Amino Acids
; 40(3): 781-92, 2011 Mar.
Article
en En
| MEDLINE
| ID: mdl-20640461
Protein glycosylation on serine/threonine residues with N-acetylglucosamine (O-GlcNAc) is a dynamic, inducible and abundant post-translational modification. It is thought to regulate many cellular processes and there are examples of interplay between O-GlcNAc and protein phosphorylation. In metazoa, a single, highly conserved and essential gene encodes the O-GlcNAc transferase (OGT) that transfers GlcNAc onto substrate proteins using UDP-GlcNAc as the sugar donor. Specific inhibitors of human OGT would be useful tools to probe the role of this post-translational modification in regulating processes in the living cell. Here, we describe the synthesis of novel UDP-GlcNAc/UDP analogues and evaluate their inhibitory properties and structural binding modes in vitro alongside alloxan, a previously reported weak OGT inhibitor. While the novel analogues are not active on living cells, they inhibit the enzyme in the micromolar range and together with the structural data provide useful templates for further optimisation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
N-Acetilglucosaminiltransferasas
/
Inhibidores Enzimáticos
Límite:
Humans
Idioma:
En
Revista:
Amino Acids
Asunto de la revista:
BIOQUIMICA
Año:
2011
Tipo del documento:
Article
Pais de publicación:
Austria