Synthesis and anti-human immunodeficiency virus type 1 activities of new peptido-nucleoside analogues
Synthesis and anti-human immunodeficiency virus type 1 activities of new peptido-nucleoside analogues
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新型肽核苷类似物的合成及其抗人类免疫缺陷病毒1型活性
DOI：
10.1016/0223-5234(96)88298-5
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发表时间：
1995
影响因子：
6.7
通讯作者：
J. Kraus
中科院分区：
文献类型：
--
作者：
M. Camplo;V. Niddam;P. Barthélémy;P. Faury;N. Mourier;Viviana Simon;A. Charvet;C. Trabaud;J. Graciet;J. Chermann;J. Kraus
为了研究与抗逆转录酶核苷偶联的抗蛋白酶肽是否可以在 HIV 生命周期的不同阶段充当抑制剂，使用涉及（苯并三唑-1-基氧基）-三（二甲氨基）鏻六氟磷酸盐（BOP）作为 N4-胞嘧啶基部分和肽羧基末端之间的偶联试剂的方法合成了各种肽核苷。测定了此类新型化合物在 MT4 细胞中的抗 HIV-1 活性及其抗 HIV 蛋白酶活性。已合成了 14 种肽核苷，其中 6 种在体外可对抗 HIV 蛋白酶和病毒复制。尽管发现最有效的抗 HIV 化合物的活性比母体核苷药物 2',3'-二脱氧-3'-硫胞苷低一个数量级，但这一类新化合物可能具有生物学意义。事实上，由于人血浆中最有效的化合物水解的体外半衰期 (t1/2) 超过 2.5 小时，因此这些类似物可以以其结构完整性到达受感染的细胞。这一观察结果并不排除这些化合物可能作为组合前药通过细胞外或细胞内水解发挥其抗病毒作用。
In order to investigate whether antiproteasic peptides coupled to anti-reverse transcriptase nucleosides can act as inhibitors at the different stages of the HIV life cycle, various peptido-nucleosides were synthesized using methodologies involving (benzotriazol-1-yloxy)-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) as a coupling reagent between the N4-cytosinyl moiety and the peptide carboxy terminus. The anti-HIV-1 activity in MT4cells of this new class of compounds and their anti-HIV protease activities were determined. Fourteen peptido-nucleosides have been synthesized and six act against both the HIV-protease and viral replication in vitro. Although the activity of the most potent compounds against HIV was found to be one order of magnitude lower than that of the parent nucleoside drug 2′,3′-dideoxy-3′-thiacytidine, this new class of compound could be of biological interest. Indeed, since the in vitro half-lives (t1/2) of the hydrolysis of the most potent compounds in human plasma were found to be longer than 2.5 h, these analogues could reach the infected cells in their structural integrity. This observation does not exclude that these compounds may exert their antiviral effects as combined prodrugs through extracellular or intracellular hydrolysis.
人类免疫缺陷病毒 1 型 (HIV-1) 蛋白酶抑制剂 Ro 31-8959 与齐多夫定、2,3-双脱氧胞苷或重组干扰素-α A 之间在体外对齐多夫定敏感或耐药的 HIV-1 的抑制相互作用。
DOI：
10.1093/infdis/166.5.1143
发表时间：
1992
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Johnson,VA;Merrill,DP;Chou,TC;Hirsch,MS
通讯作者：
Hirsch,MS
影响因子：
7.3
作者：
AGGARWAL, SK;GOGU, SR;AGRAWAL, KC
通讯作者：
AGRAWAL, KC
研究含有 4-氨基-3-羟基-5-苯基戊酸异构体的抑制剂与 HIV-1 蛋白酶结合的立体化学。
DOI：
10.1016/s0006-291x(05)81274-4
发表时间：
1991
影响因子：
3.1
作者：
Raju,B;Deshpande,MS
通讯作者：
Deshpande,MS