Synthesis and properties of oligonucleotides containing a 7-membered (oxepane) sugar ring.
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 degrees C. The oxepane oligonucleotides were also found to associate with their respective complementary RNA strands thus forming oT(15):rA(15) (13 degrees C) and oA(15):rU(15) (12 degrees 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 degrees C, 32 degrees C and 16 degrees C, respectively. The CD spectrum of oT(15):rA(15) closely resembled that of the native dT(15):rA(15) 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.
Department of Chemistry, McGill University, Montreal, Quebec, Canada.
David
D
Sabatino
Masad J
MJ
Damha
D002942:Circular Dichroism; D015195:Drug Design; D004926:Escherichia coli / Q000201:enzymology; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D010082:Oxepins / Q000737:chemistry; D016914:Ribonuclease H / Q000378:metabolism; D013816:Thermodynamics
D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D010082:Oxepins; C434331:phosphoramidite; D016914:Ribonuclease H