The long term objective of this application is to further develop two lead compounds, MAP 30 and GAP 31, which have shown three activities that may be critical to the antiviral action. These include RNA N-glycosidase, DNA topoinactivation,and HIV-integrase which are critical target in selective antiviral therapy. In the revised application Dr. Lee-Huang proposes to study the followings: Peptide fragmentation and activity mapping of MAP 30 and GAP 31 to define the domains responsible for anti-HIV activity, ribosome inactivation, DNA tipoinactivation and HIV-integrase inhibition; recombinant expression and site-specific mutagenesis to facilitate rational development of effective anti-HIV mimetic. The identification of domains responsible for these activities of MAP 30 and GAP 31 will be important in: revealing the requirements for the structure and function of these proteins; defining the extent to which these activities, or whether in all of them, contribute to the anti-HIV action; and identifying particular peptide sequences or fragment that confer anti-HIV activity. This may provide ideal therapeutic tools for the treatment of AIDS. Such defined peptides may be conveniently synthesized and easily modulated for improved efficiency. Many AIDS organizations and AIDS patient groups have expressed strong support of her work. This work may provides insight into the mechanism underlying the antiviral activity of these compounds, and will hopefully contribute to the development of clinically useful drugs.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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AIDS and Related Research Study Section 4 (ARRD)
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New York University
Schools of Medicine
New York
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Lee-Huang, Sylvia; Huang, Philip Lin; Huang, Paul Lee (2014) Live-cell real-time imaging of mitochondria in HIV-1-infected cells. AIDS Res Hum Retroviruses 30:1025-6
Li, Hui-Guang; Huang, Philip L; Zhang, Dawei et al. (2010) A new activity of anti-HIV and anti-tumor protein GAP31: DNA adenosine glycosidase--structural and modeling insight into its functions. Biochem Biophys Res Commun 391:340-5
Lee-Huang, Sylvia; Maiorov, Vladimir; Huang, Philip L et al. (2005) Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity. Biochemistry 44:4648-55
Lee-Huang, S; Huang, P L; Sun, Y et al. (2000) Inhibition of MDA-MB-231 human breast tumor xenografts and HER2 expression by anti-tumor agents GAP31 and MAP30. Anticancer Res 20:653-9
Wang, Y X; Jacob, J; Wingfield, P T et al. (2000) Anti-HIV and anti-tumor protein MAP30, a 30 kDa single-strand type-I RIP, shares similar secondary structure and beta-sheet topology with the A chain of ricin, a type-II RIP. Protein Sci 9:138-44
Wang, Y X; Neamati, N; Jacob, J et al. (1999) Solution structure of anti-HIV-1 and anti-tumor protein MAP30: structural insights into its multiple functions. Cell 99:433-42
Schreiber, C A; Wan, L; Sun, Y et al. (1999) The antiviral agents, MAP30 and GAP31, are not toxic to human spermatozoa and may be useful in preventing the sexual transmission of human immunodeficiency virus type 1. Fertil Steril 72:686-90
Huang, P L; Sun, Y; Chen, H C et al. (1999) Proteolytic fragments of anti-HIV and anti-tumor proteins MAP30 and GAP31 are biologically active. Biochem Biophys Res Commun 262:615-23
Bourinbaiar, A S; Lee-Huang, S (1996) The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against herpes simplex virus in vitro. Biochem Biophys Res Commun 219:923-9
Bourinbaiar, A S; Lee-Huang, S (1995) Acrosin inhibitor, 4'-acetamidophenyl 4-guanidinobenzoate, an experimental vaginal contraceptive with anti-HIV activity. Contraception 51:319-22

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