Effect of the structure of adenosine mimic of bisubstrate-analog inhibitors on their activity towards basophilic protein kinases

Erki Enkvist; Marie Kriisa; Mart Roben; Grete Kadak; Gerda Raidaru; Asko Uri

doi:10.1016/j.bmcl.2009.09.026

Effect of the structure of adenosine mimic of bisubstrate-analog inhibitors on their activity towards basophilic protein kinases

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6098-101. doi: 10.1016/j.bmcl.2009.09.026. Epub 2009 Sep 12.

Authors

Erki Enkvist¹, Marie Kriisa, Mart Roben, Grete Kadak, Gerda Raidaru, Asko Uri

Affiliation

¹ Institute of Chemistry, University of Tartu, 2 Jakobi St., 51014 Tartu, Estonia.

PMID: 19800227
DOI: 10.1016/j.bmcl.2009.09.026

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