A series of telbivudine 3′-O-acetyl-5′-O-phenyl-N-alkylphosphramidate derivatives have been synthesized and their structures were confirmed by El-MS, ^1H NMR and ^13C NMR. We evaluated their anti-HBV activity in vit...
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A series of telbivudine 3′-O-acetyl-5′-O-phenyl-N-alkylphosphramidate derivatives have been synthesized and their structures were confirmed by El-MS, ^1H NMR and ^13C NMR. We evaluated their anti-HBV activity in vitro. Two compounds 6d and 6f, turned out to be more active than telbivudine.
目的筛选我国HIV-1B′亚型毒株中可能存在的新型耐药相关突变位点。方法收集整理本实验室前期研究获得的45l条HIV-1B′亚型pol区基因序列,序列含蛋白酶全长(1-99个密码子)和逆转录酶全长(1-560个密码子),长度约1977bp。将354条来自接受抗病毒治疗艾滋病患者的序列与97条来自未接受治疗患者的序列分别与B亚型野生型pol基因共享序列进行逐个密码子比对,筛选在治疗序列中出现的频率显著高于未治疗序列的突变位点,将筛选出来的突变位点在斯坦福大学HIV-1耐药数据库(Stanford HIV Drug Resistance Database,SHDB)中进行检索,根据数据库收录的情况及解释初步分析突变与耐药的关系。结果在逆转录酶区有6个位点7个突变在治疗患者序列中出现的频率显著高于未治疗患者,分别是D123E、V292I、K366R、T369A、T369V、A371V和I375V,前2个突变位于逆转录酶的聚合酶区、后5个突变位于逆转录酶的连接区。检索数据库收录的情况,7个突变均为相应位点的主要变异形式,在服用某些药物的患者中出现的频率显著高于未服药的患者。结论筛选出7个存在于我国HIV-1B′亚型毒株的可能与耐药有关的突变,下一步将通过构建突变病毒及药物敏感性实验鉴定突变对耐药的作用。
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