Search for substrate-based inhibitors fitting the S2' space of malarial aspartic protease plasmepsin II. |
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Authors: | Aiko Kiso Koushi Hidaka Tooru Kimura Yoshio Hayashi Azin Nezami Ernesto Freire Yoshiaki Kiso |
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Affiliation: | Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan. kiso@mb.kyoto-phu.ac.jp |
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Abstract: | Plasmepsin (Plm) has been identified as an important target for the development of new antimalarial drugs, since its inhibition leads to the starvation of Plasmodium falciparum. A series of substrate-based dipeptide-type Plm II inhibitors containing the hydroxymethylcarbonyl isostere as a transition-state mimic were synthesized. The general design principle was provision of a conformationally restrained hydroxyl group (corresponding to the set residue at the P2' position in native substrates) and a bulky unit to fit the S2' pocket. |
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Keywords: | antimalarial drug aspartic protease inhibitor plasmepsin transition‐state mimic allophenylnorstatine |
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