Oligodeoxynucleotides Containing Diastereomeric O2′,C3′‐linked Bicyclic Nucleotide Units for Functionalization of the Major Groove of Nucleic Acid Duplexes: A Summary and Novel Derivatives*

* Dedicated to the memory of professor Jacques H. van Boom.

Abstract

The synthesis and evaluation of a range of piperazino‐derivatized diastereomeric O2′,C3′‐linked bicyclic nucleotides are described. A new and optimized protocol is presented for the synthesis of the bicyclic scaffold on which the piperazino moiety is appended. At low salt concentration, the C2″‐S‐configured piperazino‐modified oligonucleotides display significantly enhanced hybridization affinity toward complementary DNA and RNA targets relative to the unmodified oligonucleotide control, whereas no melting transition is observed for hybrids formed with the C2″‐R‐configured piperazino‐modified oligonucleotides. Upon derivatization of the piperazino moiety with a 1‐pyrenebutanoyl group, all modified oligonucleotides display strong DNA binding and profound DNA hybridization selectivity.

* Dedicated to the memory of professor Jacques H. van Boom.

Keywords:

• Oligonucleotide
• Bicyclic nucleotide
• Fluorescence
• Pyrene
• Low salt hybridization
• DNA selectivity
• RNA selectivity

Acknowledgments

Ms. Britta M. Dahl (University of Copenhagen), Ms. Kirsten Østergaard, and Ms. Suzy W. Lena are thanked for oligonucleotide synthesis and oligonucleotide purification. The Danish National Research Foundation and the Danish Research Agency are thanked for financial support.

Notes

* Dedicated to the memory of professor Jacques H. van Boom.