Novel inhibitor-based photoaffinity labeling and MALDI mass spectrometry for identification of anti-malarial drug targets

摘要

We have recently identified two series of compounds based on aspartic protease inhibitors having nanomolar potency against P. falciparum. Some of these compounds were found to have good antimalarial efficacy in-vivo. To further our understanding of mechanism, photoaffinity probes based on lead inhibitors were synthesized and used in an attempt to identify sites of interaction in P. falciparum infected erythrocytes. The use of a photoaffinity analog with strong antimalarial potency combined with affinity isolation of labeled proteins and progress toward their identification by MALDI mass spectrometry and database searching is described.