Sparks M A, Williams K W, Whitesides G M
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
J Med Chem. 1993 Mar 19;36(6):778-83. doi: 10.1021/jm00058a016.
Copolymers consisting of a polyacrylamide backbone with side chains terminated in C-glycosidic analogs of N-acetylneuraminic acid were synthesized by free radical copolymerization of alpha-2-C-[3-[[2-(N-acryloylamino)ethyl]thio]propyl]-N- acetylneuraminic acid (5) with acrylamide. Unlike natural and synthetic polyvalent materials that contain N-acetylneuraminic acid in O-glycosidic form, these C-glycosidic copolymers resist neuraminidase-catalyzed cleavage of the neuraminic acid residue from the copolymer backbone. Examination of these C-glycosidic copolymers in a hemagglutination inhibition assay indicated that they are as effective in vitro as polyvalent O-glycosidic copolymers in inhibiting agglutination of erythrocytes by influenza virus. The minimum value of the inhibition constant, calculated on the basis of the concentration of Neu5Ac groups in solution, is Ki(HAI) approximately 10(-7) M for both copolymers. The inhibitory potency of the C-glycoside-based copolymers becomes more significant at lower concentrations of Neu5Ac moieties in solution than does the inhibitory potency of the O-glycoside-based copolymer.
由聚丙烯酰胺主链和以N-乙酰神经氨酸的C-糖苷类似物为末端的侧链组成的共聚物,是通过α-2-C-[3-[[2-(N-丙烯酰基氨基)乙基]硫代]丙基]-N-乙酰神经氨酸(5)与丙烯酰胺的自由基共聚反应合成的。与以O-糖苷形式含有N-乙酰神经氨酸的天然和合成多价材料不同,这些C-糖苷共聚物能抵抗神经氨酸酶催化的神经氨酸残基从共聚物主链上的裂解。在血凝抑制试验中对这些C-糖苷共聚物的检测表明,它们在体外抑制流感病毒对红细胞的凝集作用方面与多价O-糖苷共聚物一样有效。根据溶液中Neu5Ac基团的浓度计算,两种共聚物的抑制常数最小值为Ki(HAI)约10(-7)M。与基于O-糖苷的共聚物相比,基于C-糖苷的共聚物在溶液中较低浓度的Neu5Ac部分时抑制效力更显著。