title: Cryptosporidium parvum metalloaminopeptidase inhibitors prevent in vitro excystation.
abstract: Cryptosporidium parvum arginine aminopeptidase (RAP) was studied during in vitro excystation. Specific RAP inhibitors were identified by using C. parvum extracts. Amastatin, a series of alpha-aminoboronic acids, and the chelating agents EDTA and 1,10-phenanthrolene, but not endoproteinase inhibitors, blocked enzymatic activity. RAP inhibitors found to be effective in soluble enzymatic assays were then studied for their effect on in vitro excystation. 1,10-Phenanthrolene, amastatin, and H-boronorleucine (pinacol) inhibited excystation by 84, 57, and 61%, respectively, compared with solvent-treated control oocysts. Sporozoites remained viable within the oocyst as determined by propidium iodide and fluorescein diacetate dye uptake, suggesting that alpha-aminoboronic acids were not directly lethal to the parasite.
authors.affiliation: Department of Internal Medicine, Medical School and Center for Infectious Diseases, School of Public Health, University of Texas Health Science Center, Houston 77030, USA. Okhuysen@heart.med.uth.tmc.edu
authors.forename: P C
authors.initials: PC
authors.lastname: Okhuysen
authors.forename: C L
authors.initials: CL
authors.lastname: Chappell
authors.forename: C
authors.initials: C
authors.lastname: Kettner
authors.forename: C R
authors.initials: CR
authors.lastname: Sterling
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001897:Boronic Acids / Q000032:analysis / Q000494:pharmacology; D016785:Cryptosporidium parvum / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004492:Edetic Acid / Q000494:pharmacology; D010455:Peptides; D010618:Phenanthrolines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D013170:Spores / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001897:Boronic Acids; D010455:Peptides; D010618:Phenanthrolines; D011480:Protease Inhibitors; C016977:amastatin; D004492:Edetic Acid; D000626:Aminopeptidases; C019721:aminopeptidase B; C025205:1,10-phenanthroline