Discovery of Novel Epoxyketone Peptides as Lipase Inhibitors.
Molecules
; 27(7)2022 Mar 31.
Article
in English
| MEDLINE | ID: covidwho-1785838
ABSTRACT
Obesity is the most common nutritional disorder in the developed world and is associated with important comorbidities. Pancreatic lipase (PL) inhibitors play a key role in the metabolism of human fat. A series of novel epoxyketones peptide derivatives were investigated for their pancreatic lipase inhibitory activity. The epoxyketone moiety is a well-known reactive electrophile group that has been used as part of proteasome inhibitors in cancer therapy, and it is widely believed that these are very selective for targeting the proteasome active site. Here we investigated various peptide derivatives with an epoxide warhead for their anti-lipase activity. The assessment of these novel epoxyketones was performed by an in-house method that we developed for rapid screening and identification of lipase inhibitors using GC-FID. Herein, we present a novel anti-lipase pharmacophore based on epoxyketone peptide derivatives that showed potent anti-lipase activity. Many of these derivatives had comparable or more potent activity than the clinically used lipase inhibitors such as orlistat. In addition, the lipase appears to be inhibited by a wide range of epoxyketone analogues regardless of the configuration of the epoxide in the epoxyketone moiety. The presented data in this study shows the first example of the use of epoxyketone peptides as novel lipase inhibitors.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptides
/
Proteasome Inhibitors
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal subject:
Biology
Year:
2022
Document Type:
Article
Affiliation country:
Molecules27072261
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