Vitamin E-Conjugated Phosphopeptide Inhibitor of the Polo-Box Domain of Polo-Like Kinase 1.
Antineoplastic Agents
/ chemistry
Apoptosis
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Cell Cycle Proteins
/ metabolism
Cell Survival
/ drug effects
Enzyme Activation
/ drug effects
Flow Cytometry
HeLa Cells
Humans
Mitosis
/ drug effects
Phosphopeptides
/ chemistry
Protein Serine-Threonine Kinases
/ metabolism
Proto-Oncogene Proteins
/ metabolism
Vitamin E
/ chemistry
Polo-Like Kinase 1
PLHS[pT]
cancer
polo-box domain
polo-like kinase 1
vitamin E conjugate
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
02 12 2019
02 12 2019
Historique:
pubmed:
31
10
2019
medline:
25
7
2020
entrez:
31
10
2019
Statut:
ppublish
Résumé
Polo-like kinase 1 (Plk1) regulates cell cycle and cell proliferation, and is currently considered a potential biomarker in clinical trials for many cancers. A characteristic feature of Plks is their C-terminal polo-box domain (PBD). Pro-Leu-His-Ser-pThr (PLHS[pT])-the phosphopeptide inhibitor of the PBD of Plk1-induces apoptosis in cancer cells. However, because of the low cell membrane-penetration ability of PLHS[pT], new approaches are required to overcome these drawbacks. We therefore developed a vitamin E (VE) conjugate that is biodegradable by intracellular redox enzymes as an anticancer drug-delivery system. To ensure high efficiency of membrane penetration, we synthesized VE-S-S-PLHS[pT]KY (
Identifiants
pubmed: 31663746
doi: 10.1021/acs.molpharmaceut.9b00757
doi:
Substances chimiques
Antineoplastic Agents
0
Cell Cycle Proteins
0
Phosphopeptides
0
Proto-Oncogene Proteins
0
Vitamin E
1406-18-4
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM