Srivastava O P, Hindsgaul O, Shoreibah M, Pierce M
Department of Chemistry, University of Alberta, Edmonton, Canada.
Carbohydr Res. 1988 Aug 15;179:137-61. doi: 10.1016/0008-6215(88)84115-6.
Six analogs of the trisaccharide 8-methoxycarbonyloctyl 6-O-[2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-alpha-D-mannopyrano syl] -beta-D-mannopyranoside (3), a previously reported acceptor for N-acetylglucosaminyltransferase-V (GnT-V) have been chemically synthesized and evaluated as GnT-V acceptors. Replacement of the beta-D-man rho-O(CH2)8COOMe "reducing end" of 3 by beta-D-Glc rho-O(CH2)7 CH3 gave octyl 6-O-[2-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl]-alpha-D- mannopyranosyl)-beta-D-glucopyranoside (5) whose activity was indistinguishable from that of 3. Removal of the 4-OH group of the beta-D-Glc residue in 5 had little effect on the activity, while the corresponding 4-O-methyl derivative was twice as active. Replacement of the C-6 pro-R hydrogen of the same residue by a methyl group gave the L-glycero-D-gluco derivative 8, whereas replacement of the corresponding pro-S hydrogen gave the D-glycero-D-gluco compound 9. Trisaccharide 8, whose rotameric distribution about the C-5-C-6 bond is sterically biased towards the gg conformation was less than half as active as 5 as a GnT-V acceptor, whereas 9, which is biased towards the gt conformation, was more than twice as active. These results provide evidence for the conformational control of oligosaccharide biosynthesis.
已化学合成了三糖8-甲氧羰基辛基6-O-[2-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基)-α-D-甘露吡喃糖基]-β-D-甘露吡喃糖苷(3)的六种类似物，3是先前报道的N-乙酰葡糖胺基转移酶-V(GnT-V)的受体，并将其作为GnT-V受体进行了评估。用β-D-葡萄糖基-O(CH2)7CH3取代3的β-D-甘露糖基-O(CH2)8COOMe“还原端”，得到辛基6-O-[2-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基]-α-D-甘露吡喃糖基)-β-D-吡喃葡萄糖苷(5)，其活性与3的活性无明显差异。去除5中β-D-葡萄糖残基的4-OH基团对活性影响不大，而相应的4-O-甲基衍生物的活性是其两倍。将同一残基的C-6前-R氢用甲基取代，得到L-甘油-D-葡萄糖衍生物8，而将相应的前-S氢取代，得到D-甘油-D-葡萄糖化合物9。三糖8围绕C-5-C-6键的旋转异构体分布在空间上偏向gg构象，作为GnT-V受体，其活性不到5的一半，而偏向gt构象的9的活性则是其两倍多。这些结果为寡糖生物合成的构象控制提供了证据。
