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Kensaku Anraku
Department Kumamoto Health Science University Department of Medical Technology, Faculty of Health Science Kumamoto Health Science University Graduate School Division of Health Sciences, Graduate School of Health Sciences Position Professor |
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| Date | 2019/05/21 |
| Presentation Theme | DESIGN AND SYNTHESIS OF PHOSPHOLIPID DERIVATIVES EXHIBITING HIGH-AFFINITY BINDING FOR THE HIV-1 MA DOMAIN |
| Conference | Retroviruses |
| Promoters | Cold Spring Harbor Laboratory |
| Conference Type | International |
| Presentation Type | Poster |
| Contribution Type | Collaborative |
| Venue | Cold Spring Harbor, USA |
| Publisher and common publisher | Kensaku Anraku, Hiroshi Tateishi, Kazuaki Monde, Ryota Fukuda, Ryoko Koga, Kotaro Koiwai, Fumiaki Yumoto, Toshiya Senda, Shogo Misumi, Masami Otsuka, and Mikako Fujita |
| Details | The viral protein Pr55Gag is one of the products produced by hijacked host cells and mediates HIV-1 virion budding. As Pr55Gag-PIP2 binding triggers the virion budding, we considered that a small molecule that binds firmly to Pr55Gag could antagonize PIP2 in the Pr55Gag binding. We synthesized an artificial phosphoinositide, L-HIPPO (L-Heptanoylphosphatidyl Inositol Pentakisphosphate). L-HIPPO-α-CDE (cyclodextrin-dendridimer conjugate) complex suppressed membrane localization of Pr55Gag and subsequent virus release and induced apoptosis of the host cell.
In development of L-HIPPO, we also found that one of host cell’s phospholipid, cardiolipin (CL) binds to MA domain stronger than PIP2, and CL inhibited HIV-1 infectivity at low concentration. We designed and synthesized of CL derivatives, and these derivatives bound to MA domain with relative high affinity. |