Abstract
A series of open-chain analogs of cyclic peptides was designed and synthesized using sansalvamide A as a model compound. All compounds exhibited low antitumor activity. Furthermore, the evaluation of their inhibitory potency toward IMPDH, SHP2, ACHE, proteasome, MAGL, and cathepsin B showed that all of the compounds were potent against protein tyrosine phosphatase Shp2. Specifically, compounds 1a, 1d, 2b, and 2f were found to inhibit SHP2 with IC50 values in the low micromolar range and good selectivity. Based on the molecular docking results, the binding modes of the chain cyclic peptides in the active center of SHP2 were discussed.
Keywords:
Chain peptides; Inhibitory activity; Molecular docking; SHP2; Synthesis.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylcholinesterase / chemistry
-
Catalytic Domain
-
Cathepsin B / antagonists & inhibitors
-
Cathepsin B / chemistry
-
Cell Line, Tumor
-
Cell Proliferation / drug effects
-
Enzyme Assays
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / pharmacology
-
GPI-Linked Proteins / antagonists & inhibitors
-
GPI-Linked Proteins / chemistry
-
Gene Expression
-
HeLa Cells
-
Humans
-
IMP Dehydrogenase / antagonists & inhibitors
-
IMP Dehydrogenase / chemistry
-
Kinetics
-
Molecular Docking Simulation
-
Peptides, Cyclic / chemical synthesis*
-
Peptides, Cyclic / pharmacology
-
Proteasome Endopeptidase Complex / drug effects
-
Proteasome Endopeptidase Complex / metabolism
-
Protein Binding
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / antagonists & inhibitors*
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11 / chemistry
-
Structure-Activity Relationship
Substances
-
Enzyme Inhibitors
-
GPI-Linked Proteins
-
Peptides, Cyclic
-
IMP Dehydrogenase
-
IMPDH1 protein, human
-
ACHE protein, human
-
Acetylcholinesterase
-
PTPN11 protein, human
-
Protein Tyrosine Phosphatase, Non-Receptor Type 11
-
Cathepsin B
-
Proteasome Endopeptidase Complex