Synthesis of peptidomimetics and chemo-biological tools for CD95/PLCγ1 interaction analysis.
CD95
Cell migration
Fas
Lupus
PPI inhibitor
Phospholipase
Th17
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
24
05
2019
revised:
28
06
2019
accepted:
02
07
2019
pubmed:
16
7
2019
medline:
21
10
2020
entrez:
15
7
2019
Statut:
ppublish
Résumé
The death receptor CD95 (also known as Fas) induces apoptosis through protein/protein association and the formation of the death-inducing signaling complex. On the other hand, in certain biological conditions, this receptor recruits different proteins and triggers the formation of another complex designated motility-inducing signaling complex, which promotes cell migration and inflammation. This pathway relies on a short sequence of CD95, called calcium-inducing domain (CID), which interacts with the phospholipase PLCγ1. To better understand how CID/PLCγ1 interaction occurs, we synthesized different α-AA peptides mimicking CID. Some of these peptidomimetics are as potent as the natural peptide to disrupt the CID/PLCγ1 interaction and cell migration, and showed improved pharmacokinetic properties. We also generated biotinyl- and palmitoyl-labelled peptidomimetics, useful chemico-biological tools to further explore the pro-inflammatory signal of CD95, which plays an important role in the pathogenesis of lupus and other autoimmune diseases.
Identifiants
pubmed: 31301931
pii: S0960-894X(19)30451-2
doi: 10.1016/j.bmcl.2019.07.006
pii:
doi:
Substances chimiques
FAS protein, human
0
Peptidomimetics
0
fas Receptor
0
Biotin
6SO6U10H04
PLCG1 protein, human
EC 3.1.4.11
Phospholipase C gamma
EC 3.1.4.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2094-2099Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.