Abstract
Previously reported structural fragments that associate with the ATP-binding pocket of basophilic protein kinases were conjugated with d-arginine-containing peptides. Inhibitory potency of the resulting bisubstrate-analog inhibitors towards PKA and ROCK-II extended to subnanomolar range. The conjugates incorporating 2-pyrimidyl-5-amidothiophene fragment had the highest activity and at 100 nM concentration exhibited over 80% inhibition of most of the tested basophilic kinases of the AGC group.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenosine / analogs & derivatives*
-
Adenosine / chemistry
-
Arginine / chemistry
-
Binding Sites
-
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
-
Cyclic AMP-Dependent Protein Kinases / metabolism
-
Peptides / chemical synthesis
-
Peptides / chemistry
-
Peptides / pharmacology
-
Protein Binding
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry*
-
Protein Kinase Inhibitors / pharmacology
-
Pyrimidines / chemistry
-
Thiophenes / chemistry
-
rho-Associated Kinases / antagonists & inhibitors*
-
rho-Associated Kinases / metabolism
Substances
-
Peptides
-
Protein Kinase Inhibitors
-
Pyrimidines
-
Thiophenes
-
Arginine
-
rho-Associated Kinases
-
Cyclic AMP-Dependent Protein Kinases
-
Adenosine
-
pyrimidine