| Structure-Based Design, Synthesis, of Human Cyclophilin Inhibitors |
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Presentation: P01004 Session: Cheminformatics, Library Design and Virtual HTS - Poster SessionJean-Francois Guichou, Julien Viaud, Yea-Lih Lin, Dominique Douguet, Guy Subra, Clement Mettling and Alain Chavanieu, Centre de Biochimie Structurale Presenting Author: Jean-Francois Guichou, Centre de Biochimie Structurale - France Cyclophilins belong to the family of peptidylprolyl-isomerase (PPIase) enzymes that regulate protein folding and transport. Cytosolic human cyclophilin A (hCypA) is the most abundant form and is the target for the immunosuppressant drug cyclosporin A (CsA). The discovery that inhibition of cyclophilin prevents its incorporation into the HIV protein coat suggests that families of inhibitors unrelated to the immunosuppressant cyclosporins may have anti-HIV activity. In order to identify inhibitory molecules of CypA, a structure-based design approach was used for selecting the initial compound library destined for virtual screening. Here, we report the lead identification through virtual screening and the synthesis of a series of non-peptidic cyclophilin ligands, along with their in vitro anti-HIV activity. |