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Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides
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 an...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182329/ https://www.ncbi.nlm.nih.gov/pubmed/16077030 http://dx.doi.org/10.1093/nar/gki743 |
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author | Tripathi, Snehlata Chaubey, Binay Ganguly, Sabyasachi Harris, Dylan Casale, Ralph A Pandey, Virendra N. |
author_facet | Tripathi, Snehlata Chaubey, Binay Ganguly, Sabyasachi Harris, Dylan Casale, Ralph A Pandey, Virendra N. |
author_sort | Tripathi, Snehlata |
collection | PubMed |
description | 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 (PNA(TAR)) 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 PNA(TAR)–peptide conjugates where uptake of the PNA(TAR)–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 IC(50) values in the range of 28–37 nM while IC(50) for inhibition of HIV-1 replication was lowest with PNA(TAR)–transportan-27 (0.4 μM) followed by PNA(TAR)–tat (0.72 μM) and PNA(TAR)–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. |
format | Text |
id | pubmed-1182329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-11823292005-08-03 Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides Tripathi, Snehlata Chaubey, Binay Ganguly, Sabyasachi Harris, Dylan Casale, Ralph A Pandey, Virendra N. Nucleic Acids Res Article 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 (PNA(TAR)) 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 PNA(TAR)–peptide conjugates where uptake of the PNA(TAR)–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 IC(50) values in the range of 28–37 nM while IC(50) for inhibition of HIV-1 replication was lowest with PNA(TAR)–transportan-27 (0.4 μM) followed by PNA(TAR)–tat (0.72 μM) and PNA(TAR)–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. Oxford University Press 2005 2005-08-02 /pmc/articles/PMC1182329/ /pubmed/16077030 http://dx.doi.org/10.1093/nar/gki743 Text en © The Author 2005. Published by Oxford University Press. All rights reserved |
spellingShingle | Article Tripathi, Snehlata Chaubey, Binay Ganguly, Sabyasachi Harris, Dylan Casale, Ralph A Pandey, Virendra N. Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides |
title | Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides |
title_full | Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides |
title_fullStr | Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides |
title_full_unstemmed | Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides |
title_short | Anti-HIV-1 activity of anti-TAR polyamide nucleic acid conjugated with various membrane transducing peptides |
title_sort | anti-hiv-1 activity of anti-tar polyamide nucleic acid conjugated with various membrane transducing peptides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182329/ https://www.ncbi.nlm.nih.gov/pubmed/16077030 http://dx.doi.org/10.1093/nar/gki743 |
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