Improved Cell-Potent and Selective Peptidomimetic Inhibitors of Protein N-Terminal Methyltransferase 1.
cell-permeable inhibitor
peptidomimetic inhibitor
protein N-terminal methyltransferase
structure-based drug design
Journal
Molecules (Basel, Switzerland)
ISSN: 1420-3049
Titre abrégé: Molecules
Pays: Switzerland
ID NLM: 100964009
Informations de publication
Date de publication:
18 Feb 2022
18 Feb 2022
Historique:
received:
21
12
2021
revised:
29
01
2022
accepted:
01
02
2022
entrez:
25
2
2022
pubmed:
26
2
2022
medline:
3
3
2022
Statut:
epublish
Résumé
Protein N-terminal methyltransferase 1 (NTMT1) recognizes a unique N-terminal X-P-K/R motif (X represents any amino acid other than D/E) and transfers 1-3 methyl groups to the N-terminal region of its substrates. Guided by the co-crystal structures of NTMT1 in complex with the previously reported peptidomimetic inhibitor DC113, we designed and synthesized a series of new peptidomimetic inhibitors. Through a focused optimization of DC113, we discovered a new cell-potent peptidomimetic inhibitor GD562 (IC
Identifiants
pubmed: 35209173
pii: molecules27041381
doi: 10.3390/molecules27041381
pmc: PMC8874984
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Peptidomimetics
0
Methyltransferases
EC 2.1.1.-
NTMT1 protein, human
EC 2.1.1.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM117275
Pays : United States
Organisme : National Institute of Health
ID : GM117275
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