Toki D, Granovsky M A, Reck F, Kuhns W, Baker M A, Matta K L, Brockhausen I
Department of Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada.
Biochem Biophys Res Commun. 1994 Jan 28;198(2):417-23. doi: 10.1006/bbrc.1994.1061.
Cells from patients with acute myeloid leukaemia (AML) contain an abnormally high UDP-GlcNAc: Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase (core 2 beta 6-Gn-T) activity. Upon UV irradiation at 350 nm, the substrate Gal beta 1-3GalNAc alpha-p-nitrophenyl acted as an effective inhibitor for this enzyme but not for several other transferases. Preincubation with Gal beta 1-3GalNAc alpha-benzyl but not GalNAc alpha-benzyl protected core 2 beta 6-Gn-T from inhibition indicating that the inhibitor is specific for the substrate binding site of core 2 beta 6-Gn-T. A number of other nitrophenyl-sugar derivatives similarly acted as inhibitors for core 2 beta 6-Gn-T. GalNAc alpha-pnp at higher concentrations also inactivated UDP-Gal: GalNAc-R beta 3-galactosyltransferase from rat liver and AML cells and inhibition could be reduced by substrate protection. These results suggest that pnp-sugar derivatives may prove useful as specific inhibitors of glycosyltransferases and as affinity labels.
急性髓系白血病（AML）患者的细胞中，UDP-葡萄糖胺：Galβ1-3GalNAc-R（GlcNAc到GalNAc）β6-N-乙酰葡糖胺转移酶（核心2 β6-Gn-T）活性异常高。在350nm紫外线照射下，底物Galβ1-3GalNAcα-对硝基苯作为该酶的有效抑制剂，但对其他几种转移酶无效。用Galβ1-3GalNAcα-苄基而非GalNAcα-苄基预孵育可保护核心2 β6-Gn-T免受抑制，表明该抑制剂对核心2 β6-Gn-T的底物结合位点具有特异性。许多其他硝基苯基糖衍生物同样可作为核心2 β6-Gn-T的抑制剂。较高浓度的GalNAcα-pnp还可使大鼠肝脏和AML细胞中的UDP-Gal：GalNAc-R β3-半乳糖基转移酶失活，底物保护可降低抑制作用。这些结果表明，对硝基苯基糖衍生物可能作为糖基转移酶的特异性抑制剂和亲和标记物有用。
