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Journal of Virology, March 2004, p. 2637-2641, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2637-2641.2003
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of Peptides That Inhibit the DNA Binding, trans-Activator, and DNA Replication Functions of the Human Papillomavirus Type 11 E2 Protein

Su-Jun Deng,1 Kenneth H. Pearce,1 Eric P. Dixon,2 Kelly A. Hartley,3 Thomas B. Stanley,1 David C. Lobe,4 Edward P. Garvey,5 Thomas A. Kost,1 Regina L. Petty,5 Warren J. Rocque,1 Kenneth A. Alexander,3,6* and Mark R. Underwood4*

Departments of Gene Expression and Protein Biochemistry,1 Molecular Pharmacology,2 Molecular Screening,5 Clinical Virology, GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709,4 Departments of Microbiology,3 Pediatrics, Duke University Medical Center, Durham, North Carolina 277106

Received 27 September 2002/ Accepted 7 November 2003

Peptide antagonists of the human papillomavirus type 11 (HPV-11) E2-DNA association were identified using a filamentous bacteriophage random peptide library. Synthetic peptides antagonized the E2-DNA interaction, effectively blocked E2-mediated transcriptional activation of a reporter gene in cell culture, and inhibited E1-E2-mediated HPV-11 DNA replication in vitro. These peptides may prove to be useful tools for characterizing E2 function and for exploring the effectiveness of E2-inhibitor-based treatments for HPV-associated diseases.

* Corresponding author. Mailing address for Kenneth A. Alexander: Department of Microbiology, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-9590. Fax: (919) 684-8735. E-mail: kenneth.alexander{at}duke.edu. Mailing address for Mark R. Underwood: Department of Clinical Virology, GlaxoSmithKline Research and Development, 5 Moore Dr., Research Triangle Park, NC 27709. Phone: (919) 483-9151. Fax: (919) 315-5243. E-mail: mark.r.underwood{at}gsk.com.

Journal of Virology, March 2004, p. 2637-2641, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2637-2641.2003
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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