Chemical modification of the glucosidase inhibitor 1-deoxynojirimycin. Structure-activity relationships.
Chemical modification of the glucosidase inhibitor 1-deoxynojirimycin. Structure-activity relationships.
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葡萄糖苷酶抑制剂1-脱氧野尻霉素的化学修饰。
DOI：
10.1016/s0021-9258(18)98715-6
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
J. Bolscher
中科院分区：
文献类型：
--
作者：
A. Tan;L. V. D. van den Broek;S. V. van Boeckel;H. Ploegh;J. Bolscher
研究了葡萄糖苷酶抑制剂1-脱氧野尻霉素（dNM）和一系列N-烷基化dNM衍生物干扰HepG 2细胞中糖蛋白α 1-抗胰蛋白酶的生物合成、转运和成熟的能力。dNM及其衍生物对内质网葡萄糖苷酶I和II的抑制导致α 1-抗胰蛋白酶与含葡萄糖的高甘露糖型寡糖（前体）在细胞内蓄积。N-烷基化的dNM增加其抑制内质网葡糖苷酶的效力，从所需的浓度为最大抑制的一半。dNM的N-烷基化衍生物能够比葡糖苷酶II更好地抑制葡糖苷酶I（从保留在Endo H-可释放寡糖中的葡萄糖残基的数量推断）。烷基化dNM衍生物对葡萄糖苷酶活性的抑制作用比dNM更不容易逆转，N-甲基-dNM的效果最明显。dNM衍生物的烷基基团的支化降低了抑制效力。尽管dNM及其衍生物强烈干扰细胞内寡糖加工，但即使在最高检测浓度下，它们也不能完全阻断α 1-抗胰蛋白酶的N-聚糖成熟。
The ability of the glucosidase inhibitor 1-deoxynojirimycin (dNM) and a series of N-alkylated dNM derivatives to interfere with biosynthesis, transport, and maturation of the glycoprotein alpha 1-antitrypsin in HepG2 cells was investigated. Inhibition of endoplasmic reticulum glucosidase I and II by dNM and its derivatives resulted in an intracellular accumulation of alpha 1-antitrypsin with glucose-containing high mannose type oligosaccharides (precursor). N-alkylation of dNM increased its potency in inhibiting endoplasmic reticulum glucosidases, as determined from the concentration required for half maximal inhibition. N-Alkylated derivatives of dNM were better able to inhibit glucosidase I than glucosidase II (deduced from the number of glucose residues retained in Endo H-releasable oligosaccharides). The inhibition of glucosidase activity imposed by alkylated dNM derivatives was less easily reversed than that by dNM, an effect most pronounced for N-methyl-dNM. Branching of the alkyl group of dNM derivatives decreased the inhibitory potency. Although dNM and its derivatives interfered strongly with intracellular oligosaccharide processing, they did not completely block N-glycan maturation of alpha 1-antitrypsin even at the highest concentrations tested.
DOI：
10.1016/s0021-9258(19)45358-1
发表时间：
1982-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Brigitte Saunier;R. Kilker;Jan S. Tkaczq;Andrea Quaronill;A. Herscovics
通讯作者：
Brigitte Saunier;R. Kilker;Jan S. Tkaczq;Andrea Quaronill;A. Herscovics
证明高尔基体内切-α-D-甘露糖苷酶为糖蛋白的复杂 N-连接寡糖的形成提供了独立于葡萄糖苷酶的途径。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Moore,SE;Spiro,RG
通讯作者：
Spiro,RG
α-葡萄糖苷酶和外切-α-葡聚糖酶对 D-葡萄糖水合的立体化学研究：糖基酶催化中可塑相和保守相的迹象。
影响因子：
2.9
作者：
Chiba,S;Brewer,CF;Okada,G;Matsui,H;Hehre,EJ
通讯作者：
Hehre,EJ