Hydroxyl-Functionalized DNA: An Efficient Orthogonal Protecting Strategy and Duplex Stability

Abstract

Tert-butyldiphenylsilyl (TBDPS) was found to be an effective orthogonal protecting strategy for the 5-substituted hydroxyl groups of de novo synthesized deoxyuridine analogues 1–3 and 7-(3-hydroxypropynyl)- of 8-aza-7-deazadeoxyadenosine 4 for their incorporation into oligodeoxynucleotides by phosphoramidite chemistry. It could be completely cleaved under normal and ultra-mild deprotection conditions applied to DNA synthesis, without extra cleaving operation. The new phosphoramidites were coupled as usual with high yields. The new modified oligodeoxynucleotides were characterized by MALDI-TOF and enzymatic cleavage analysis. The thermal stability and conformation of these hydroxyl-functionalized DNA duplexes were evaluated.

Keywords:

• Hydroxyl
• TBDPS
• nucleosides
• DNA
• functionalization

Acknowledgments

Financial support by Beijing Institute of Pharmacology and Toxicology is gratefully acknowledged.

Notes

^aMeasured in (D₆)DMSO at 303 K.

^bPyrimidine base numbering.

^cTentative.

^dSystematic numbering for purine base.

^eSuperimposed by (D₆)DMSO.

^aMeasured in 100 mM NaCl, 10 mM MgCl₂, and 10 mM Na-cacodylate (pH 7.0) with 5 μM oligonucleotides.