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Inhibition of Moloney murine leukemia virus integration using polyamides targeting the long-terminal repeat sequences

Yang, Fan and Belitsky, Jason M. and Villanueva, Rodrigo A. and Dervan, Peter B. and Roth, Monica J. (2003) Inhibition of Moloney murine leukemia virus integration using polyamides targeting the long-terminal repeat sequences. Biochemistry, 42 (20). pp. 6249-6258. ISSN 0006-2960. doi:10.1021/bi034177s.

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The retroviral integrase (IN) carries out the integration of the viral DNA into the host genome. Both IN and the DNA sequences at the viral long-terminal repeat (LTR) are required for the integration function. In this report, a series of minor groove binding hairpin polyamides targeting sequences within terminal inverted repeats of the Moloney murine leukemia virus (M-MuLV) LTR were synthesized, and their effects on integration were analyzed. Using cell-free in vitro integration assays, polyamides targeting the conserved CA dinucleotide with cognate sites closest to the terminal base pairs were effective at blocking 3' processing but not strand transfer. Polyamides which efficiently inhibited 3' processing and strand transfer targeted the LTR sequences through position 9. Polyamides that inhibited integration were effective at nanomolar concentrations and showed subnanomolar affinity for their cognate LTR sites. These studies highlight the role of minor groove interactions within the LTR termini for retroviral integration.

Item Type:Article
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Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 2003 American Chemical Society. Received January 31, 2003. Publication Date (Web): May 2, 2003.
Issue or Number:20
Record Number:CaltechAUTHORS:20160510-080154263
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Official Citation:Inhibition of Moloney Murine Leukemia Virus Integration Using Polyamides Targeting the Long-Terminal Repeat Sequences Fan Yang, Jason M. Belitsky, Rodrigo A. Villanueva, Peter B. Dervan, and Monica J. Roth Biochemistry 2003 42 (20), 6249-6258 DOI: 10.1021/bi034177s
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66803
Deposited By: Victoria Brennan
Deposited On:18 May 2016 00:29
Last Modified:11 Nov 2021 00:03

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