title: Development of bestatin-based activity-based probes for metallo-aminopeptidases.
abstract: A novel set of activity-based probes (ABPs) for functionally profiling metallo-aminopeptidases was synthesized based on the bestatin inhibitor scaffold, the first synthesis of bestatin analogues using solid-phase techniques. These ABPs were shown to label metallo-aminopeptidases, using both a biotin and a fluorophore reporter, in an activity-dependent manner. This probe class was also shown to be amenable to 'click' chemistry labeling for possible use in live cells. Finally, we demonstrate that the ABPs are able to label an aminopeptidase in a complex proteome. Thus, these bestatin-based probes should have wide utility to functionally profile aminopeptidases in many biological systems.
authors.affiliation: University of Pennsylvania, Department of Pharmacology, 433 S. University Avenue, 304G Lynch Laboratories, Philadelphia, PA 19104-6018, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Harbut
authors.forename: Geetha
authors.initials: G
authors.lastname: Velmourougane
authors.forename: Gilana
authors.initials: G
authors.lastname: Reiss
authors.forename: Rajesh
authors.initials: R
authors.lastname: Chandramohanadas
authors.forename: Doron C
authors.initials: DC
authors.lastname: Greenbaum
mesh_terms: D000626:Aminopeptidases / Q000378:metabolism*; D020134:Catalytic Domain; D005456:Fluorescent Dyes; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D005456:Fluorescent Dyes; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex