TITLE

Structure�Activity of Inhibition of HIV-1 Integrase and Virus Replication by G-quartet Oligonucleotides

AUTHOR(S)
Jing, Naijie; Marchand, Christophe; Guan, Yongli; Liu, Jie; Pallansch, Luke; Lackman-Smith, Carol; De Clercq, Erik; Pommier, Yves
PUB. DATE
August 2001
SOURCE
DNA & Cell Biology;Aug2001, Vol. 20 Issue 8, p499
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
As novel anti-HIV agents, the G-tetrad-forming oligonucleotides have been explored for their structure�activity relations with regard to inhibition of integrase (IN) (N. Jing, Expert Opin. Investig. Drugs (2000) 9, 1777�1785). We have now developed two families of G-quartet oligonucleotides: T40217�T40222, with potential formation of a tail-to-tail G-quartet dimer, and T40224�T40227, with phosphorothioate (PT) linkages in the guanine loops. The results obtained from biophysical measurements and the assays of the inhibition of HIV-1 IN and virus replication demonstrated that an increase in the length of the G-quartet structure from a monomer (15�) to a tail-to-tail dimer (47�) does not distinctly disrupt the inhibition of HIV-1 IN activity or the inhibition of HIV-1 replication in cell cultures. G-quartet oligonucleotides were observed to induce molecular aggregation of HIV-1 IN and interrupt the binding of viral DNA to HIV-1 IN. Also, PT substitutions did not confer any advantages compared with the regular phosphodiesters for the inhibition of HIV-1 replication by intramolecular G-quartets. The G-quartet motif is the primary requirement for the remarkable nuclease resistance and pronounced biological efficacy of these oligonucleotides.
ACCESSION #
5322758

 

Related Articles

  • Bioelectronic DNA detection of human papillomaviruses using eSensor: a model system for detection of multiple pathogens. Vernon, Suzanne D.; Farkas, Daniel H.; Unger, Elizabeth R.; Chan, Vivian; Miller, Donna L.; Yin-Peng Chen; Blackburn, Gary F.; Reeves, William C. // BMC Infectious Diseases;2003, Vol. 3 Issue 1, p12 

    Background: We used human papillomaviruses (HPV) as a model system to evaluate the utility of a nucleic acid, hybridization-based bioelectronic DNA detection platform (eSensorâ„¢) in identifying multiple pathogens. Methods: Two chips were spotted with capture probes consisting of DNA...

  • Molecular genetic analysis of Mycobacterium tuberculosis strains spread in different patient groups in St. Petersburg, Russia. Chernyaeva, E.; Dobrynin, P.; Pestova, N.; Matveeva, N.; Zhemkov, V.; Kozlov, A. // European Journal of Clinical Microbiology & Infectious Diseases;Aug2012, Vol. 31 Issue 8, p1753 

    Molecular epidemiological features of Mycobacterium tuberculosis strains among different patient groups in Russia have not been studied well. The aim of our study was to compare the genotypes of M. tuberculosis strains circulating among tuberculosis (TB) patients from different groups: homeless,...

  • High-throughput real-time assay based on molecular beacons for HIV-1 integrase 3′-processing reaction. Hong-qiu He; Xiao-hui Ma; Bin Liu; Xiao-yi Zhang; Wei-zu Chen; Cun-xin Wang; Shao-hui Cheng // Acta Pharmacologica Sinica;Jun2007, Vol. 28 Issue 6, p811 

    Aim: To develop a high-throughput real-time assay based on molecular beacons to monitor the integrase 3′-processing reaction in vitro and apply it to inhibitor screening. Methods: The recombinant human immunodeficiency virus (HIV)-1 integrase (IN) is incubated with a 38 mer oligonucleotide...

  • Inhibition of HIV-1 integrase by modified oligonucleotides: Optimization of the inhibitor structure. Prikazchikova, T. A.; Volkov, E. M.; Zubin, E. M.; Romanova, E. A.; Gottikh, M. B. // Molecular Biology;Jan2007, Vol. 41 Issue 1, p118 

    Integration of human immunodeficiency virus type 1 DNA into the infected cell genome is one of the key steps of the viral replication cycle. Therefore, viral integrase is of interest as a target for new antiviral drugs. Conjugates of 11-mer single-stranded oligonucleotides with hydrophobic...

  • Inhibition of the Human Immunodeficiency Virus Type 1 DNA Integration by Modified Oligonucleotides. Pinskaya, M. D.; Brodin, P.; Romanova, E. A.; Volkov, E. M.; Mouscadet, J.-F.; Gottikh, M. B. // Molecular Biology;Nov2000, Vol. 34 Issue 6, p888 

    Oligonucleotide inhibitors of the HIV-1 DNA integration identified to date are reviewed. Two basic strategies of blocking the integration are considered: shielding the integrase-binding sites on the viral DNA by triplex-forming oligonucleotides, and directly inhibiting the enzyme with...

  • Characterization of Recombinant Integrase of Human Immunodeficiency Virus Type 1 (Isolate Bru). Semenova, E. A.; Gashnikova, N. M.; Il'ina, T. V.; Pronyaeva, T. R.; Pokrovsky, A. G. // Biochemistry (00062979);Sep2003, Vol. 68 Issue 9, p988 

    Integration of the human immunodeficiency virus type 1 (HIV-1) DNA into the human genome requires the virusencoded integrase protein. The recombinant integrase protein of HIV-1 (isolate Bru) was prepared by constructing a plasmid based on pET-15b encoding the integrase gene. Integrase of HIV-1...

  • Interaction of HIV-1 Reverse Transcriptase with Modified Oligonucleotide Primers Containing 2′-O-β-D-Ribofuranosyladenosine. Golubeva, A. S.; Ermolinsky, B. S.; Efimtseva, E. V.; Tunitskaya, V. L.; van Aerschot, A.; Herdewijn, P.; Mikhailov, S. N.; Kochetkov, S. N. // Biochemistry (00062979);Feb2004, Vol. 69 Issue 2, p130 

    Modified synthetic oligodeoxyribonucleotides containing 2′-O-β-D-ribofuranosyladenosine were used as primers in the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase. The degree of elongation of the primers depends on the position of the additional ribose unit, its...

  • Polymorphisms of the human IFNG gene noncoding regions. Bream, Jay H.; Carrington, Mary; O’Toole, Stefanie; Dean, Michael; Gerrard, Bernard; Hyoung Doo Shin; Kosack, Daniel; Modi, William; Young, Howard A.; Smith, Michael W. // Immunogenetics;Jan2000, Vol. 51 Issue 1, p50 

    Interferon gamma (IFN-gamma) is a multifunctional cytokine that is essential in the development of Th1 cells and in cellular responses to a variety of intracellular pathogens including human immunodeficiency virus (HIV-1). We screened genomic DNA samples from a predominately Caucasian male...

  • Surface plasmon resonance study on HIV-1 integrase strand transfer activity. Vaisocherová, Hana; Snášel, Jan; Špringer, Tomáš; Šípová, Hana; Rosenberg, Ivan; Štìpánek, Josef; Homola, Jiří // Analytical & Bioanalytical Chemistry;Feb2009, Vol. 393 Issue 4, p1165 

    Understanding the molecular mechanism of HIV-1 integrase (IN) activity is critical to find functional inhibitors for an effective AIDS therapy. A robust, fast, and sensitive method for studying IN activity is required. In this work, an assay for real-time label-free monitoring of the IN activity...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics