Lopalco L, Ciccomascolo F, Lanza P, Zoppetti G, Caramazza I, Leoni F, Beretta A, Siccardi A G
Centro San Luigi, Istituto Scientifico H San Raffaele, Milan, Italy.
AIDS Res Hum Retroviruses. 1994 Jul;10(7):787-93. doi: 10.1089/aid.1994.10.787.
Several groups have reported that sulfated polysaccharides are potent and selective in vitro inhibitors of human immunodeficiency virus type 1 (HIV-1); however, their therapeutic application is limited by their anticoagulant activity. In view of possible improvements in therapeutic potential, a number of heparin derivatives with reduced anticoagulant activity were studied for their inhibitory activity of an HIV-dependent syncytium formation assay, in comparison with standard anionic polysaccharides, such as sodium heparin, dextran sulfate, and heparin sulfate. The chemical modifications introduced in the heparin molecule included succinylation of desulfated N groups (Suc-H), exhaustive periodate oxidation and reduction (RO-H), and controlled nitrous acid degradation (LMW-H). The most pronounced anti-HIV activity was observed with RO-H, Suc30-H (standard heparin, 30% succinylated), and Suc100-LMW-H (low molecular weight heparin, 100% succinylated); the latter retained only 5% of the anticoagulant activity of standard heparin, whereas RO-H and Suc30-H retained approximately 35% of the anticoagulant activity of standard heparin. A safety ratio (arbitrary units of anti-HIV activity per anticoagulant international unit) was calculated: by this parameter, RO-H, Suc30-H, and Suc100-LMW-H were, respectively, 48-, 3.6-, and 1644-fold more safe than standard heparin.
几个研究小组报告称，硫酸化多糖是1型人类免疫缺陷病毒（HIV-1）强大且具有选择性的体外抑制剂；然而，它们的治疗应用受到其抗凝活性的限制。鉴于治疗潜力可能的改善，研究了一些抗凝活性降低的肝素衍生物在HIV依赖性合胞体形成试验中的抑制活性，并与标准阴离子多糖，如肝素钠、硫酸葡聚糖和硫酸肝素进行比较。在肝素分子中引入的化学修饰包括脱硫酸化N基团的琥珀酰化（Suc-H）、高碘酸彻底氧化和还原（RO-H）以及可控的亚硝酸降解（LMW-H）。观察到RO-H、Suc30-H（标准肝素，30%琥珀酰化）和Suc100-LMW-H（低分子量肝素，100%琥珀酰化）具有最显著的抗HIV活性；后者仅保留了标准肝素抗凝活性的5%，而RO-H和Suc30-H保留了标准肝素抗凝活性的约35%。计算了安全比（每抗凝国际单位的抗HIV活性任意单位）：根据该参数，RO-H、Suc30-H和Suc100-LMW-H分别比标准肝素安全48倍、3.6倍和1644倍。
