Abstract：
:Aspartyl aminopeptidase (DNPEP) has been implicated in the control of angiotensin signaling and endosome trafficking, but its precise biologic roles remain incompletely defined. We performed a high-throughput screen of ∼25,000 small molecules to identify inhibitors of DNPEP for use as tools to study its biologic functions. Twenty-three confirmed hits inhibited DNPEP-catalyzed hydrolysis of angiotensin II with micromolar potency. A counter screen against glutamyl aminopeptidase (ENPEP), an enzyme with substrate specificity similar to that of DNPEP, identified eight DNPEP-selective inhibitors. Structure-activity relationships and modeling studies revealed structural features common to the identified inhibitors, including a metal-chelating group and a charged or polar moiety that could interact with portions of the enzyme active site. The compounds identified in this study should be valuable tools for elucidating DNPEP physiology.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Chen Y,Tang H,Seibel W,Papoian R,Oh K,Li X,Zhang J,Golczak M,Palczewski K,Kiser PDdoi
10.1124/mol.114.093070subject
Has Abstractpub_date
2014-08-01 00:00:00pages
231-42issue
2eissn
0026-895Xissn
1521-0111pii
mol.114.093070journal_volume
86pub_type
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