Inhibition of UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase from acute myeloid leukaemia cells by photoreactive nitrophenyl substrate derivatives.
Inhibition of UDP-GlcNAc:Gal beta 1-3GalNAc-R (GlcNAc to GalNAc) beta 6-N-acetylglucosaminyltransferase from acute myeloid leukaemia cells by photoreactive nitrophenyl substrate derivatives.
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光反应性硝基苯基底物衍生物抑制急性髓系白血病细胞中的 UDP-GlcNAc:Gal beta 1-3GalNAc-R（GlcNAc 至 GalNAc）β 6-N-乙酰氨基葡萄糖转移酶。
DOI：
10.1006/bbrc.1994.1061
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发表时间：
1994
影响因子：
3.1
通讯作者：
Brockhausen,I
中科院分区：
文献类型：
--
作者：
Toki,D;Granovsky,MA;Reck,F;Kuhns,W;Baker,MA;Matta,KL;Brockhausen,I
急性髓系白血病患者的细胞含有异常高的UDP-GlcNAc：Galβ1-3Ga1NAc-R(GlcNAc到GalNAc)β6-N-乙酰氨基葡萄糖转移酶(核心2β6-Gn-T)。在紫外光照射下，底物半乳糖β1-3GalNAcα-对硝基苯基是该酶的有效抑制物，但对其他几种转移酶无抑制作用。用Galβ1-3GalNAcα-苄基预孵育，而不用GalNAcα-苄基预孵育，可以保护核心2β6-Gn-T不受抑制，表明该抑制剂是针对核心2β6-Gn-T底物结合部位的。一些其他的硝基苯糖衍生物类似地作为核心2β6-Gn-T的抑制剂。较高浓度的α-PNP对大鼠肝脏和急性髓系白血病细胞的UDPGal：GalNAc-Rβ3-半乳糖基转移酶也有失活作用，底物保护可使抑制作用减弱。这些结果表明，PNP-糖衍生物可能被证明是有用的糖基转移酶的特定抑制剂和亲和标记。
Cells from patients with acute myeloid leukaemia (AML) contain an abnormally high UDP-GlcNAc:Galβ1-3Ga1NAc-R (GlcNAc to GalNAc) β6-N-acetylglucosaminyltransferase (core 2 β6-Gn-T) activity. Upon UV irradiation at 350 nm, the substrate Galβ1-3GalNAcα-p-nitrophenyl acted as an effective inhibitor for this enzyme but not for several other transferases. Preincubation with Galβ1-3GalNAcα-benzyl but not GalNAcα-benzyl protected core 2 β6-Gn-T from inhibition indicating that the inhibitor is specific for the substrate binding site of core 2 β6-Gn-T. A number of other nitrophenyl-sugar derivatives similarly acted as inhibitors for core 2 β6-Gn-T. GalNAcα-pnp at higher concernrations also inactivated UDP-Gal: GalNAc-R β3-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 affmity labels.