Screening aspartyl proteases with combinatorial libraries.
Large numbers of pharmaceutically relevant low-molecular weight compounds can now be synthesized using combinatorial methods. Screening these large libraries of compounds requires high throughput assays. These methods are utilized to search for inhibitors of the aspartyl proteases, plasmepsin II and cathepsin D. Plasmepsin II, a protease found in the malaria parasite, hydrolyzes human hemoglobin, the nutrient source for the parasite and is a new target for anti-malaria therapy. Cathepsin D may be involved in many biological processes and inhibitors would help to clarify the role of cathepsin D in these processes. Plasmepsin II and cathepsin D are approximately 35% identical in amino acid sequence. Therefore, a comparison of the screening results of these two enzymes will be very useful in determining each enzyme's specificity and demonstrating the power of utilizing encoded combinatorial libraries.
Carroll
C D
CD
Pharmacopeia, Inc., Princeton, New Jersey 08540, USA.
Orlowski
M
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D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000138:chemical synthesis / Q000378:metabolism*; D002402:Cathepsin D / Q000138:chemical synthesis / Q000378:metabolism*; D006801:Humans; D015800:Protozoan Proteins
D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II; D002402:Cathepsin D