Synthesis and Anti-HIV Activity of Sulfated Oligosaccharide-Branched β-CD
Synthesis and Anti-HIV Activity of Sulfated Oligosaccharide-Branched β-CD
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DOI：
10.2115/fiberst.2020-0006
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发表时间：
2020-01-01
影响因子：
0.6
通讯作者：
Yoshida, Takashi
中科院分区：
文献类型：
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作者：
Bai Mingxue;Chaolumen, Bai;Yoshida, Takashi
将乙酰化的1-O-丙基-β-D-麦芽糖苷与庚烷-6-叠氮基-β-CD进行点击反应，合成了6-O-麦芽糖基-β-CD，再经脱乙酰基反应合成了6-O-麦芽糖基-β-CD(6-O-heptakis-6-[4-(beta-D-maltopyranosyloxymethyl)-1H-1，-β-CD)。以6-O-葡萄糖基-β-环糊精为原料合成了6-O-葡萄糖-β-环糊精。这些硫化的β-CD具有较强的抗HIV活性(EC50)，分别为1.3和27.9微克/毫升，然而，硫化的β-CD的抗HIV活性较低，为200微克/毫升。以多聚L赖氨酸作为HIV表面糖蛋白GP 120模型的表面等离子体共振谱表明，表观结合常数k(A)增大，解离速率常数k(D)减小，分别为k(A)=0.21×10(3)，6.24×10(3)，1.46×10(4)1/ms和k(D)=6.70×10(-4)，3.92×10(-4)，3.03×10(-4)1/S。动态光散射法测定其粒径分别为13.7 nm、6.2 nm和3.3 nm。这些结果表明，硫化β-CD的颗粒大小也对抗HIV活性的强度起到了重要作用。由于6-O-麦芽糖基-β-CD的粒径(13.7 nm)比HIV-GP 120(8~10 nm)稍大，6-O-麦芽糖基-β-CD与HIV gp 120的静电相互作用表现出最强的抗HIV活性。
Sulfated heptakis-6-[4-(beta-D-maltopyranosyloxymethyl)-1H-1, 2, 3- triazoyl-1-yl)-beta-CD (6-O-maltosyl beta-CD) was prepared by the sulfation of 6-O-maltosyl beta-CD that had been synthesized by click reaction of acetylated 1-O-propagyl-beta-D-maltoside with heptakis-6-azido beta-CD and then deacetylation. Sulfated 6-O-glucosyl beta-CD was also synthesized from 6-O-glucosyl beta-CD. These sulfated beta-CDs were found to have potent anti-HIV activity (EC50) of 1.3 and 27.9 mu g/mL, respectively, however, sulfated beta-CD had low anti-HIV activity,>200 mu g/mL. The surface plasmon resonance against poly-L-lysine as a model of HIV surface glycoprotein gp 120 indicated that the apparent association- (k(a)) and dissociation-rate (k(d)) constants increased and decreased, respectively, k(a)=0.21x10(3), 6.24x10(3), 1.46x10(4) 1/Ms and k(d)=6.70x10(-4), 3.92x10(-4), 3.03x10(-4) 1/s, by depending on the number of branched glucose units. The particle size of the sulfated beta-CDs was 13.7 nm, 6.2 nm, and 3.3 nm,respectively, measured by dynamic light scattering. These results suggest that the particle size of the sulfated beta-CDs also played an important role in the strength of anti-HIV activity. The highest anti-HIV activity of sulfated 6-O-maltosyl beta-CD was expressed by the electrostatic interaction with HIV gp 120 putting on sulfated 6-O-maltosyl beta-CD like a cap, because the particle size (13.7 nm) was somewhat larger than that of HIV gp 120 (8 to 10 nm).