Carbocyclic 3'-deoxyadenosine-based highly potent bisubstrate-analog inhibitor of basophilic protein kinases

Erki Enkvist; Gerda Raidaru; Angela Vaasa; Tõnis Pehk; Darja Lavogina; Asko Uri

doi:10.1016/j.bmcl.2007.08.016

Carbocyclic 3'-deoxyadenosine-based highly potent bisubstrate-analog inhibitor of basophilic protein kinases

Bioorg Med Chem Lett. 2007 Oct 1;17(19):5336-9. doi: 10.1016/j.bmcl.2007.08.016. Epub 2007 Aug 15.

Authors

Erki Enkvist¹, Gerda Raidaru, Angela Vaasa, Tõnis Pehk, Darja Lavogina, Asko Uri

Affiliation

¹ Institute of Organic and Bioorganic Chemistry, University of Tartu, 2 Jakobi Street, 51014 Tartu, Estonia.

PMID: 17716894
DOI: 10.1016/j.bmcl.2007.08.016

Abstract

Carbocyclic analogs of 3'-deoxyadenosine were synthesized as racemates and the resulting stereoisomers were separated by chromatography on a chiral column. The conjugation of obtained compounds with hexa-(D-arginine) via 6-aminohexanoic acid linker led to a highly potent inhibitor of several basophilic protein kinases with some selectivity towards cAMP-dependent protein kinase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenine / analogs & derivatives*
Adenine / chemical synthesis
Adenine / pharmacology
Adenosine Triphosphate / metabolism
Aminocaproic Acid / chemistry
Arginine / chemistry
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Cyclopentanes / chemical synthesis*
Cyclopentanes / pharmacology*
Fluorometry
Kinetics
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / pharmacology*
Stereoisomerism
Structure-Activity Relationship
Substrate Specificity

Substances

Cyclopentanes
Protein Kinase Inhibitors
carbocyclic deoxyadenosine
Adenosine Triphosphate
Arginine
Cyclic AMP-Dependent Protein Kinases
Adenine
Aminocaproic Acid