Synthesis and Properties of Oligonucleotides Containing A 7-Membered (Oxepane) Sugar Ring

Abstract

Herein we describe the synthesis of novel 7-membered ring (oxepane) thymine and adenine nucleosides (oT and oA) and their corresponding 5′-O-phosphoramidite derivatives. Two homopolymeric sequences (oT 15 and oA 15 ) were prepared via conventional solid-phase synthesis. The mutually complementary strands had the ability to form a duplex (oT 15 :oA 15 ) exhibiting a transition temperature of 12°C. The oxepane oligonucleotides were also found to associate with their respective complementary RNA strands thus forming oT 15 :rA 15 (13°C) and oA 15 :rU 15 (12°C) hybrids. The corresponding native duplexes, namely dT 15 :dA 15 , dT 15 :rA 15 and dA 15 :rU 15 had melting temperatures of 37°C, 32°C and 16°C, respectively. The CD spectrum of oT 15 :rA 15 closely resembled that of the native dT 15 :rA15 hybrid and, in fact, both were found to be substrates for E. Coli RNase H. Thus the oxepane nucleic acids reported here are one of only a handful of DNA mimics capable of activating RNase H when bound to RNA.