New type anti-HIV reagents on the basis of broad substrate specificity of HIV-1 reverse transcriptase

基于HIV-1逆转录酶广泛底物特异性的新型抗HIV试剂

• 批准号: 05671832
• 负责人: SHOJI Shozo
• 金额: $ 1.34万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671832/
• 关键词: AIDS; HIV-1; HIV-1 RT; AZT; Virus; transcriptase; LAV

Attempts to overcome HIV-1 infection have been made on the basis of the points of attack of the HIV-1 life cycle. HIV-1 reverse transcriptase (RT) plays a central role in the HOV-1 life cycle, copying the genetic information in the genomic RNA into a double-stranded DNA form.Azidothymidine (AZT), an inhibitor of HIV-RT,is being used to treat AIDS.As in vitro and in vivo HIV-1 resistance to a number of RT inhibitors has been reported, RT inhibitors are shown to be no longer chemotherapy for AIDS.A kind of diketopiperazine derivatives is found to be a good or pure substrate, which is not a HIV-1 RT inhibitor, for HIV-1 RT in vitro. These results suggest that the diketopiperazine derivative is metabolically converted to a mimic nucleotide derivative in cell, transcripted to HIV-1 cDNA,and incorporated into host DNA.The mechanism of the anti-HIV action with the derivative is not understood so far, however, the new compound may be very important for AIDS chemotherapy.

已经根据HIV-1生命周期的攻击点进行了克服HIV-1感染的尝试。HIV-1逆转录酶（RT）在HOV-1生命周期中发挥着核心作用，将基因组RNA中的遗传信息复制到双链DNA形式。叠氮胸苷（AZT）是一种HIV-RT抑制剂，正在用于治疗艾滋病。随着体外和体内HIV-1对多种RT抑制剂产生耐药性的报道，逆转录酶抑制剂已不再是艾滋病的化疗药物，一种二酮哌嗪衍生物在体外是一种良好的或纯的HIV-1逆转录酶底物，它不是HIV-1逆转录酶抑制剂。这些结果表明，二酮哌嗪衍生物在细胞内代谢转化为模拟核苷酸衍生物，转录为HIV-1cDNA，并掺入宿主DNA中，其抗HIV作用的机制目前尚不清楚，但该新化合物可能对艾滋病化疗非常重要。

项目成果

Furuishi Kazuchika: "The role of the gag protein myristoylation in HIV-1 production" Thenth International Conference on AIDS. 1. 109 (1994)

Furuishi Kazuchika：“gag 蛋白肉豆蔻酰化在 HIV-1 产生中的作用”，第二届国际艾滋病会议。

K.Furuishi, H.Oh-ishi, S.Misumi, H.Matsuoka, S.Ikeda, Y.Hantani, H.Ashizawa, and S.Shoji: "The role of the gag protein myristoylation in HIV-1 producton." Tenth International Conference on AIDS. 1. 109 (1994)

K.Furuishi、H.Oh-ishi、S.Misumi、H.Matsuoka、S.Ikeda、Y.Hantani、H.Ashizawa 和 S.Shoji：“gag 蛋白肉豆蔻酰化在 HIV-1 产生中的作用。”

Furuishi Kazuchika: "The role of the gag protein myristoy lation in HIV-1 production" Thenth International Conference on AIDS. 1. 109 (1994)

Furuishi Kazuchika：“gag 蛋白肉豆蔻酰化在 HIV-1 产生中的作用”，第二届国际艾滋病会议。

R.Azuma.K.Furuishi, A.Saito, H.Sihnagawa, S.Ikeda, and S.Shoji: "The cytoskeltal proteins cleaving activity of the recombinant HIV-1 protease." Tenth International Conference on AIDS. 1. 110 (1994)

R.Azuma.K.Furuishi、A.Saito、H.Sihnakawa、S.Ikeda 和 S.Shoji：“重组 HIV-1 蛋白酶的细胞骨架蛋白裂解活性。”

Shoji Shozo: "Anti-HIV effects ofredox reagents on HIV-1 infected cell lines" Thenth International Conference on AIDS. 2. 114 (1994)

Shoji Shozo：“氧化还原试剂对 HIV-1 感染细胞系的抗 HIV 作用”，第二届国际艾滋病会议。