| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 28, 21460-21467, July 14, 2000
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the The G-tetrad-forming oligonucleotides T30177 and
T30695 have been identified as potent inhibitors of human
immunodeficiency virus type 1 integrase (HIV-1 IN) activity (Rando,
R. F., Ojwang, J., Elbaggari, A., Reyes, G. R., Tinder, R.,
McGrath, M. S., and Hogan, M. E. (1995) J. Biol.
Chem. 270, 1754-1760; Mazumder, A., Neamati, N., Ojwang, J. O., Sunder, S., Rando, R. F., and Pommier, Y. (1996)
Biochemistry 35, 13762-13771; Jing, N., and Hogan, M. E. (1998) J. Biol. Chem. 273, 34992-34999). To
understand the inhibition of HIV-1 IN activity by the G-quartet
inhibitors, we have designed the oligonucleotides T40215 and T40216,
composed of three and four G-quartets with stem lengths of 19 and 24 Å, respectively. The fact that increasing the G-quartet stem length from 15 to 24 Å kept inhibition of HIV-1 IN activity unchanged suggests that the binding interaction occurs between a GTGT loop domain
of the G-quartet inhibitors and a catalytic site of HIV-1 IN, referred
to as a face-to-face interaction. Docking the NMR structure of T30695
(Jing and Hogan (1998)) into the x-ray structure of the core domain of
HIV-1 IN, HIV-1 IN-(51-209) (Maignan, S., Guilloteau, J.-P., Qing,
Z.-L., Clement-Mella, C., and Mikol, V. (1998) J. Mol.
Biol. 282, 359-368), was performed using the GRAMM program. The
statistical distributions of hydrogen bonding between HIV-1 IN and
T30695 were obtained from the analyses of 1000 random docking
structures. The docking results show a high probability of interaction
between the GTGT loop residues of the G-quartet inhibitors and
the catalytic site of HIV-1 IN, in agreement with the experimental observation.
Mechanism of Inhibition of HIV-1 Integrase by G-tetrad-forming
Oligonucleotides in Vitro*
§,,,, and Department of Molecular Physiology and
Biophysics, Baylor College of Medicine, Houston, Texas 77030 and the
¶ Laboratory of Molecular Pharmacology, Division of Basic
Sciences, NCI, National Institutes of Health,
Bethesda, Maryland 20892-4255
*
This work was supported by National Institutes of Health
Grant GM60153 (to N. J.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Podbevsek, N. V. Hud, and J. Plavec NMR evaluation of ammonium ion movement within a unimolecular G-quadruplex in solution Nucleic Acids Res., April 11, 2007; (2007) gkm138v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.-S. Lee, K.-E. Jung, C.-H. Yoon, H. Lim, and Y.-S. Bae Newly Designed Six-Membered Azasugar Nucleotide-Containing Phosphorothioate Oligonucleotides as Potent Human Immunodeficiency Virus Type 1 Inhibitors Antimicrob. Agents Chemother., October 1, 2005; 49(10): 4110 - 4120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Phan, V. Kuryavyi, J.-B. Ma, A. Faure, M.-L. Andreola, and D. J. Patel From The Cover: An interlocked dimeric parallel-stranded DNA quadruplex: A potent inhibitor of HIV-1 integrase PNAS, January 18, 2005; 102(3): 634 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Zhou, G. Chen, Y. Wang, Q. Zhang, M. Yang, and T. Li Synthesis of unimolecularly circular G-quadruplexes as prospective molecular probes Nucleic Acids Res., December 8, 2004; 32(21): e173 - e173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Risitano and K. R. Fox Influence of loop size on the stability of intramolecular DNA quadruplexes Nucleic Acids Res., May 11, 2004; 32(8): 2598 - 2606. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Deprez, S. Barbe, M. Kolaski, H. Leh, F. Zouhiri, C. Auclair, J.-C. Brochon, M. Le Bret, and J.-F. Mouscadet Mechanism of HIV-1 Integrase Inhibition by Styrylquinoline Derivatives in Vitro Mol. Pharmacol., January 1, 2004; 65(1): 85 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Dapic, V. Abdomerovic, R. Marrington, J. Peberdy, A. Rodger, J. O. Trent, and P. J. Bates Biophysical and biological properties of quadruplex oligodeoxyribonucleotides Nucleic Acids Res., April 15, 2003; 31(8): 2097 - 2107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Facchiano, K. Russo, A. M. Facchiano, F. De Marchis, F. Facchiano, D. Ribatti, M. S. Aguzzi, and M. C. Capogrossi Identification of a Novel Domain of Fibroblast Growth Factor 2 Controlling Its Angiogenic Properties J. Biol. Chem., February 28, 2003; 278(10): 8751 - 8760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Marchand, P. Pourquier, G. S. Laco, N. Jing, and Y. Pommier Interaction of Human Nuclear Topoisomerase I with Guanosine Quartet-forming and Guanosine-rich Single-stranded DNA and RNA Oligonucleotides J. Biol. Chem., March 8, 2002; 277(11): 8906 - 8911. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
