Two lines of experiments are proposed within the Peptide Core. First, the applicant will attempt to minimize and analog the antiviral peptides currently under study. These efforts will involve the synthesis and purification of many dozens of peptides that will be tested in the three research projects. By synthesizing a series of truncated peptides, the Core Leader (CL) will identify the minimum sized peptide that is still active, and by synthesizing a series of analogs of the minimum sized peptides, the CL will discover analogs that may be resistant to proteases and which maybe more potent in their antiviral activity. This work will be supervised by Dr. Gary Case in Room 2340 of the University of Wisconsin Biotechnology Center (UWBC). Second, the CL will isolate peptide ligands by affinity selection of phage-displayed combinatorial peptide libraries to viral entry proteins that have been supplied by Drs. Brandt's, Lambert's, and Malkovsky's laboratories. Initially this work will focus on the HSV glycoproteins and HIV gpl20 and p4l. As HPV capsid proteins involved in attachment or entry are identified by other laboratories these can be used for phage display. Alternatively, viral particles could be used for selection. It should be noted that Projects I and III will focus first on the lead peptides already identified. Phage display methods will only be used for Projects I and III if time becomes available for such work. Based on the applicant's experience, phage-displayed peptide ligands typically bind at biologically active sites on protein targets, and thus peptide ligands to the viral entry proteins may have antiviral activity due to blocking attachment of viral particles to cells. This part of the Project will be supervised by Dr. Brian Kay in the Department of Pharmacology at the University of Wisconsin- Madison. The laboratories of Drs. Case and Kay are only two blocks away on campus; and these two investigators have interacted frequently over the past two years.
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