Synthesis and characterization of galactosyl lipids that bind HIV-1 gp120
AdvisorO'Brien, David F.
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PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractThe HIV-1 virus has a protein, gp120, on its surface that is responsible for the initial recognition between the virus and human cells by binding to the CD4 receptor, which is found on many types of human cells. An alternative receptor, galactosylceramide (GalCer), has also been identified. It binds to HIV-1 gp120 and facilitates the infection of human cells via a CD4 independent mechanism. The goal of this research project was to design, synthesize, and test the effectiveness of galactosyl lipids that bind to gp120. A versatile synthesis was developed and used to synthesize five different GalCer analogs. Professor Scott Saavedra and coworkers used total internal reflection fluorescence microscopy (TIRF) to measure quantitative binding affinities to gp120 at equilibrium for each glycolipid analog. A GalCer analog with octadecyl lipid chains and a tetraethylene glycol spacter group had the highest binding affinity of the analogs tested. Monolayers of lipid mixtures were investigated for phase behavior using epifluorescence microscopy. It was determined that GalCer analogs with saturated tails formed domains in monolayers with DOPC. GalCer analogs were also incorporated into liposomes and were subjected to an HIV-1 inhibition assay in Dr. Ahmad's lab. The GalCer analog liposomes showed similar inhibition as GalCer liposomes.
Degree ProgramGraduate College