Soluble Galcer Analogs as Anti-HIV Therapeutic Agents
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AbstractGalactosyl ceramide (GalCer) acts as an alternative receptor for HIV in CD4 negative cells throughto the HIV envelope glycoprotein gp 120. The design and synthesis of GalCer analogs capable of bindiblocking its interaction with GalCer is potentially a powerful therapeutic approach against HIV infesynthesize four GalCer analogs, namely, 1-O-(beta-D-galactopyranosyl)-L-threo-dihydrosphingosine, 1-galactopyranosyl)-L-erythro-dihydrosphingosine, 1-O-(beta-D- galactopyranosyl)-D-threo-dihydrosphing(beta-D- galactopyranosyl)-D-erythro-dihydrosphingosine. These four compounds were selected becausethe structural components essential for the binding to gp 120, and the lack of the fatty acid on theconsiderably their solubility in water. The ability of these analogs to bind to HIV gp 120 will be ausing HPTLC binding assays on 1251-labeled gp 120, and their ability to inhibit HIV infection will bnegative cells (e.g. SK-N-MC). We plan to study an alternative therapeutic approach, conjugating thecytotoxic compounds, and using them as targeting agents to deliver toxins selectively to HIV-infecte
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