Enhanced Biological Activity of Antisense Oligonucleotides Containing 5-(1-Hexynyl)-substituted Pyrimidine Nucleotides

E. Uhlmann Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

L. Homung Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

S. Hein Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

S. Augustin Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

A. Peyman Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

D. W. Will Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

M. Helsberg Hoechst Marion Roussel, G 838, D-65926, Frankfurt, Germany

J. Sági Hungarian Academy of Sciences, Central Research Institute for Chemistry, H-1525, Budapest, Hungary

L. Ötvös Hungarian Academy of Sciences, Central Research Institute for Chemistry, H-1525, Budapest, Hungary

J. O. Ojwang Aronex Pharmaceuticals Inc., 9391 Grogan's Mill Road, The Woodlands, Texas, 77380, U.S.A.

S. Mustain Aronex Pharmaceuticals Inc., 9391 Grogan's Mill Road, The Woodlands, Texas, 77380, U.S.A.

R. F. Rando Aronex Pharmaceuticals Inc., 9391 Grogan's Mill Road, The Woodlands, Texas, 77380, U.S.A.

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Abstract

Antisense oligonucleotides directed against HSV- 1 immediate early gene mRNA were synthesized with replacement of the internal pyrimidine nucleotides by the corresponding 5-(l-hexynyl) analogues and with end-capping by phosphorothioates. These compounds were found to have improved binding affinity, increased stability towards nucleases and enhanced antiviral activity in a cell culture assay.

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Enhanced Biological Activity of Antisense Oligonucleotides Containing 5-(1-Hexynyl)-substituted Pyrimidine Nucleotides

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Enhanced Biological Activity of Antisense Oligonucleotides Containing 5-(1-Hexynyl)-substituted Pyrimidine Nucleotides

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