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.
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