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Effect of prime-site sequence of retro-inverso-modified HTLV-1 protease inhibitor
Institution:1. Department of Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan;2. Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan;3. Department of Biochemical Engineering, Graduate School of Science and Technology, Yamagata University, Yonezawa, Yamagata 992-8510, Japan;4. Department of Chemistry, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan;1. Sapienza University of Rome, Via Salaria 113, 00198 Rome, Italy;2. INRIA, Route de Saclay, 91128 Palaiseau Cedex Inria Saclay, Ile de France, France;3. CNRS/LIP6, UPMC Sorbonne Universités, LIP6 Boîte courrier 169 Couloir 26-00, Étage 1, Bureau 109 4 Place Jussieu, 75252 Paris Cedex 05, France;1. State Key Laboratory Breeding Base for Sustainable Exploitation of Tropical Biotic Resources, College of Marine Science, Hainan University, Haikou 570228, China;2. Key Laboratory of Tropical Marine Bio-resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China;1. Department of Radiology, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea;2. Department of Neurosurgery, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea;3. Department of Neurosurgery, Science and Engineering Institute, Kyungpook National University College of Medicine, Daegu, Korea
Abstract:The effects of additional substituents covering the prime-site of retro-inverso (RI)-modified HTLV-1 protease inhibitors containing a hydroxyethylamine isoster were clarified. Stereo-selective construction of the most potent isoster backbone was achieved by the Evans-aldol reaction. Addition of N-acetylated d-amino acid corresponding to the P2′ site gave an RI-modified inhibitor showing superior inhibitory activity to the previous inhibitor. Inhibitory activities of the newly synthesized inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor.
Keywords:HTLV-1 protease  Inhibitor  Retro-inverso  Hydroxyethylamine isoster
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