期刊
CHEMBIOCHEM
卷 17, 期 16, 页码 1495-1498出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600244
关键词
bioorganic chemistry; cardiovascular system; fluorescent probes; peptides; proteases
资金
- Canadian Institutes of Health Research [CIHR 136921]
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Alberta Innovates Health Solutions (AIHS)
- Alberta Innovates [201500694] Funding Source: researchfish
The apelinergic system is a mammalian peptide hormone network with key physiological roles. Apelin isoforms and analogues are believed to be promising therapeutics for cardiovascular disease. Despite extensive studies on apelin-13 degradation patterns, only one protease, angiotensin-converting enzyme 2 (ACE2), had been implicated in its physiological regulation. Through use of a peptide-based fluorescent probe, we identified the metalloprotease neprilysin (NEP, a target for Entresto used in treatment of heart failure) as an enzyme that cleaves apelin isoforms. In vitro NEP proteolysis generated fragments that lacked the ability to bind to the apelin receptor, thereby making NEP the first protease to fully inactivate apelin. The involvement of NEP in the apelinergic system contributes to the understanding of its role in cardiovascular physiology.
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