Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides.
Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides.
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DOI：
10.1093/nar/gki743
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发表时间：
2005
影响因子：
14.9
通讯作者：
Pandey VN
中科院分区：
文献类型：
--
作者：
Tripathi S;Chaubey B;Ganguly S;Harris D;Casale RA;Pandey VN
存在于HIV-1基因组5 ' -NTR中的转录激活子反应区（TAR）是抗逆转录病毒干预的潜在靶点，也是开发rna -蛋白相互作用特异性抑制剂的模型系统。在此之前，我们已经证明了一种与膜转导（MTD）肽结合的抗tar聚酰胺核苷酸类似物（PNATAR）被细胞有效地吸收，并显示出强大的抗病毒和杀病毒活性[B]。张晓明，张晓明，张晓明（2005）病毒学进展[j]。在目前的通讯中，我们已经将五种不同的MTD肽，穿透素，该肽，转运蛋白-27及其两个截断的衍生物，转运蛋白-21和转运蛋白-22，结合到针对HIV-1基因组TAR区域的16mer PNA上。通过FACScan分析检测单个缀合物的摄取效率，使用放射性标记缀合物检测其摄取动力学，通过抑制HIV-1感染/复制评估病毒活性和抗病毒功效。而FACScan分析显示，所有pnatar -肽偶联物的细胞摄取与浓度有关，其中pnatar -穿透素偶联物的摄取效率最高，在浓度为200 nM的1分钟内观察到bb0 - 90%的MTD。与pnatar - transportan-21和tat-peptide结合的抗hiv病毒活性最强，IC50值在28 ~ 37 nM范围内，而与PNATAR-transportan-27 （0.4 μM）结合的抑制HIV-1复制的IC50值最低，其次是PNATAR-tat （0.72 μM）和PNATAR-penetratin （0.8 μM）。这些结果表明，与MTD肽结合的抗HIV-1 PNA不仅可以抑制HIV-1在体外的复制，而且是一种有效的杀病毒剂，可以使HIV-1病毒粒子在短暂暴露后不具有传染性。
The transactivator responsive region (TAR) present in the 5′-NTR of the HIV-1 genome represents a potential target for antiretroviral intervention and a model system for the development of specific inhibitors of RNA–protein interaction. Earlier, we have shown that an anti-TAR polyamide nucleotide analog (PNATAR) conjugated to a membrane transducing (MTD) peptide, transportan, is efficiently taken up by the cells and displays potent antiviral and virucidal activity [B. Chaubey, S. Tripathi, S. Ganguly, D. Harris, R. A. Casale and V. N. Pandey (2005) Virology, 331, 418–428]. In the present communication, we have conjugated five different MTD peptides, penetratin, tat peptide, transportan-27, and two of its truncated derivatives, transportan-21 and transportan-22, to a 16mer PNA targeted to the TAR region of the HIV-1 genome. The individual conjugates were examined for their uptake efficiency as judged by FACScan analysis, uptake kinetics using radiolabeled conjugate, virucidal activity and antiviral efficacy assessed by inhibition of HIV-1 infection/replication. While FACScan analysis revealed concentration-dependent cellular uptake of all the PNATAR–peptide conjugates where uptake of the PNATAR–penetratin conjugate was most efficient as >90% MTD was observed within 1 min at a concentration of 200 nM. The conjugates with penetratin, transportan-21 and tat-peptides were most effective as an anti-HIV virucidal agents with IC50 values in the range of 28–37 nM while IC50 for inhibition of HIV-1 replication was lowest with PNATAR–transportan-27 (0.4 μM) followed by PNATAR–tat (0.72 μM) and PNATAR–penetratin (0.8 μM). These results indicate that anti-HIV-1 PNA conjugated with MTD peptides are not only inhibitory to HIV-1 replication in vitro but are also potent virucidal agents which render HIV-1 virions non-infectious upon brief exposure.
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影响因子：
7.6
作者：
Kaushik, N;Basu, A;Pandey, VN
通讯作者：
Pandey, VN
影响因子：
4.8
作者：
Derossi, D;Calvet, S;Prochiantz, A
通讯作者：
Prochiantz, A
影响因子：
17.3
作者：
BUCHARDT, O;EGHOLM, M;NIELSEN, PE
通讯作者：
NIELSEN, PE
影响因子：
19
作者：
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通讯作者：
Prochiantz, A
影响因子：
4.9
作者：
Creagh, T;Ruckle, JL;Xu, ZQ
通讯作者：
Xu, ZQ