Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Tripathi, Snehlata, Chaubey, Binay, Ganguly, Sabyasachi, Harris, Dylan, Casale, Ralph A, Pandey, Virendra N.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2005
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
_version_ 1782124651735941120
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
work_keys_str_mv AT tripathisnehlata antihiv1activityofantitarpolyamidenucleicacidconjugatedwithvariousmembranetransducingpeptides
AT chaubeybinay antihiv1activityofantitarpolyamidenucleicacidconjugatedwithvariousmembranetransducingpeptides
AT gangulysabyasachi antihiv1activityofantitarpolyamidenucleicacidconjugatedwithvariousmembranetransducingpeptides
AT harrisdylan antihiv1activityofantitarpolyamidenucleicacidconjugatedwithvariousmembranetransducingpeptides
AT casaleralpha antihiv1activityofantitarpolyamidenucleicacidconjugatedwithvariousmembranetransducingpeptides
AT pandeyvirendran antihiv1activityofantitarpolyamidenucleicacidconjugatedwithvariousmembranetransducingpeptides