Ijichi K, Fujiwara M, Mori K, Morozumi M, Machida H, Shigeta S, Konno K, Yokota T, Baba M
Rational Drug Design Laboratories, Fukushima, Japan.
Antiviral Res. 1996 Jun;31(1-2):115-20. doi: 10.1016/0166-3542(96)00945-x.
Nucleotide heterodimers were synthesized and examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1), including HIV-1 reverse transcriptase (RT) inhibitor-resistant mutants. 3'-Azido-3'-deoxythymidilyl-(5')-phospho-(5')-6-[(3', 5'-dimethylphenyl)thio]-5-ethyl-1-[(2-hydroxyethoxy)methyl]uracil (AZT-P-E-HEPU-dM) and 3'-azido-3'-deoxythymidilyl-(5')-phospho-(5')-2', 3'-dideoxyinosine (AZT-P-ddI) proved to be highly potent and selective inhibitors of HIV-1 (IIIB strain) in MT-4 cells. The mechanism of inhibition by these heterodimers may be attributed to their degradation and the formation of each constituent. AZT-P-E-HEPU-dM was also markedly inhibitory to an AZT-resistant mutant (HIV-1-IIIB/AZT) and an E-HEPU-dM-resistant mutant (HIV-1-IIIB-R). However, AZT-P-ddI was found to have a less inhibitory effect on HIV-1-IIIB/AZT than on HIV-1-IIIB. The heterodimers of (5',5') AZT and ribavirin (AZT-P-Ribavirin) and (5',5') ddI and ribavirin (ddI-P-Ribavirin) were also synthesized: AZT-P-Ribavirin inhibited HIV-1 replication, but ddI-P-Ribarvirin did not.
合成了核苷酸异二聚体，并检测了它们对1型人类免疫缺陷病毒（HIV-1）复制的抑制作用，包括对HIV-1逆转录酶（RT）抑制剂耐药突变体的抑制作用。3'-叠氮-3'-脱氧胸苷基-(5')-磷酸-(5')-6-[(3',5'-二甲基苯基)硫代]-5-乙基-1-[(2-羟基乙氧基)甲基]尿嘧啶（AZT-P-E-HEPU-dM）和3'-叠氮-3'-脱氧胸苷基-(5')-磷酸-(5')-2',3'-双脱氧肌苷（AZT-P-ddI）被证明是MT-4细胞中HIV-1（IIIB株）的高效且选择性抑制剂。这些异二聚体的抑制机制可能归因于它们的降解以及各组分的形成。AZT-P-E-HEPU-dM对AZT耐药突变体（HIV-1-IIIB/AZT）和E-HEPU-dM耐药突变体（HIV-1-IIIB-R）也有明显抑制作用。然而，发现AZT-P-ddI对HIV-1-IIIB/AZT的抑制作用比对HIV-1-IIIB的抑制作用小。还合成了(5',5') AZT与利巴韦林的异二聚体（AZT-P-利巴韦林）以及(5',5') ddI与利巴韦林的异二聚体（ddI-P-利巴韦林）：AZT-P-利巴韦林抑制HIV-1复制，但ddI-P-利巴韦林没有。
