Aptameric inhibition of p210bcr-abl tyrosine kinase autophosphorylation by oligodeoxynucleotides of defined sequence and backbone structure

R Bergan; Y Connell; B Fahmy; E Kyle; L Neckers

doi:10.1093/nar/22.11.2150

Aptameric inhibition of p210bcr-abl tyrosine kinase autophosphorylation by oligodeoxynucleotides of defined sequence and backbone structure

Nucleic Acids Res. 1994 Jun 11;22(11):2150-4. doi: 10.1093/nar/22.11.2150.

Authors

R Bergan¹, Y Connell, B Fahmy, E Kyle, L Neckers

Affiliation

¹ Clinical Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Abstract

Protein tyrosine kinases play key roles in cellular physiology. Specific inhibitors of these enzymes are important laboratory tools and may prove to be novel therapeutic agents. In this report we describe a new class of tyrosine kinase inhibitor, synthetic oligodeoxynucleotides (ODNs). An ODN is described which specifically inhibits p210bcr-abl tyrosine kinase autophosphorylation in vitro with a Ki of 0.5 microM. Inhibition is non-competitive with respect to ATP. The effects upon inhibitory activity of ODN structure modifications are described. The inhibition described is not mediated by classical antisense mechanisms and represents an example of the recently recognized aptameric properties of ODNs.

MeSH terms

3T3 Cells
Animals
Base Sequence
Cell Line
DNA
Fusion Proteins, bcr-abl / antagonists & inhibitors*
Fusion Proteins, bcr-abl / metabolism
Mice
Molecular Sequence Data
Oligodeoxyribonucleotides / pharmacology*
Phosphorylation

Substances

Oligodeoxyribonucleotides
DNA
Fusion Proteins, bcr-abl