This Article Full Text (OnlineFirst PDF) All Versions of this Article: 1087057108317060v1 13/5/406    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Hou, Y. Articles by Howe, J. A. Search for Related Content PubMed PubMed Citation Articles by Hou, Y. Articles by Howe, J. A. Pubmed/NCBI databases Substance via MeSH Social Bookmarking                         What's this?

Screening for Antiviral Inhibitors of the HIV Integrase–LEDGF/p75 Interaction Using the AlphaScreen^TM Luminescent Proximity Assay

Schering-Pough Research Institute

^* To whom correspondence should be addressed. E-mail: john.howe{at}spcorp.com.

	Abstract

Small-molecule inhibitors of HIV integrase (HIV IN) have emerged as a promising new class of antivirals for the treatment of HIV/AIDS. The compounds currently approved or in clinical development specifically target HIV DNA integration and were identified using strand-transfer assays targeting the HIV IN/viral DNA complex. The authors have developed a second biochemical assay for identification of HIV integrase inhibitors, targeting the interaction between HIV IN and the cellular cofactor LEDGF/p75. They developed a luminescent proximity assay (AlphaScreen^TM) designed to measure the association of the 80-amino-acid integrase binding domain of LEDGF/p75 with the 163-amino-acid catalytic core domain of HIV IN. This assay proved to be quite robust (with a Z'factor of 0.84 in screening libraries arrayed as orthogonal mixtures) and successfully identified several compounds specific for this protein-protein interaction. (Journal of Biomolecular Screening XXXX:xx-xx)

First published on May 14, 2008, doi:10.1177/1087057108317060

Journal of Biomolecular Screening 2008;13:406.

A more recent version of this article appeared on June 1, 2008


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Tsiang, G. S. Jones, M. Hung, S. Mukund, B. Han, X. Liu, K. Babaoglu, E. Lansdon, X. Chen, J. Todd, et al. Affinities between the Binding Partners of the HIV-1 Integrase Dimer-Lens Epithelium-derived Growth Factor (IN Dimer-LEDGF) Complex J. Biol. Chem., November 27, 2009; 284(48): 33580 - 33599. [Abstract] [Full Text] [PDF]

				J. J. Kessl, J. O. Eidahl, N. Shkriabai, Z. Zhao, C. J. McKee, S. Hess, T. R. Burke Jr, and M. Kvaratskhelia An Allosteric Mechanism for Inhibiting HIV-1 Integrase with a Small Molecule Mol. Pharmacol., October 1, 2009; 76(4): 824 - 832. [Abstract] [Full Text] [PDF]

				K. Bartholomeeusen, F. Christ, J. Hendrix, J.-C. Rain, S. Emiliani, R. Benarous, Z. Debyser, R. Gijsbers, and J. De Rijck Lens Epithelium-derived Growth Factor/p75 Interacts with the Transposase-derived DDE Domain of PogZ J. Biol. Chem., April 24, 2009; 284(17): 11467 - 11477. [Abstract] [Full Text] [PDF]