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De novo Disign, Synthesis, and in vitro Evaluation of a New Class of Nonpeptidic Inhibitors of the Malarial Enzyme Plasmepsin II.

✍ Scribed by David A. Carcache; Simone R. Hoertner; Andreas Bertogg; Christoph Binkert; Daniel Bur; Hans Peter Maerki; Arnulf Dorn; Francois Diederich


Publisher
John Wiley and Sons
Year
2003
Weight
54 KB
Volume
34
Category
Article
ISSN
0931-7597

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De Novo Design, Synthesis, and In Vitro
✍ David A. Carcache; Simone R. Hörtner; Andreas Bertogg; Christoph Binkert; Daniel 📂 Article 📅 2002 🏛 John Wiley and Sons 🌐 English ⚖ 152 KB 👁 2 views

Malaria, a life-threatening disease caused by parasites of the genus Plasmodium, affects 500 million people annually, of which more than one million die. [1] The emergence of multi-drugresistant strains of Plasmodium falciparum, the parasite that causes the deadliest form of malaria, exacerbates the

Development of a New Class of Inhibitors
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## Abstract Plasmepsin II (PMII), a malarial aspartic protease involved in the catabolism of hemoglobin in parasites of the genus __Plasmodium__, and renin, a human aspartic protease, share 35% sequence identity in their mature chains. Structures of 4‐arylpiperidine inhibitors complexed to human re

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## Abstract A new class of nonpeptidic inhibitors of the malarial aspartic protease plasmepsin II (PMII) with up to single‐digit micromolar activities (__IC__~50~ values) was developed by structure‐based __de novo__ design. The active‐site matrix used in the design was based on an X‐ray crystal str

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