title: Oxepane nucleic acids: synthesis, characterization, and properties of oligonucleotides bearing a seven-membered carbohydrate ring.
abstract: The synthesis and properties of oxepane nucleic acids (ONAs) are described. ONAs are sugar-phosphate oligomers in which the pentofuranose ring of DNA and RNA is replaced with a seven-membered (oxepane) sugar ring. The oxepane nucleoside monomers were prepared from the ring expansion reaction of a cyclopropanated glycal, 1, and their conversion into phosphoramidite derivatives allowed efficient assembly of ONAs on a solid support. ONAs (oT15 and oA15) were found to be much more resistant toward nuclease degradation than natural DNA (dT15 and dA15) in fetal bovine serum (FBS) after 24 h of incubation at 37 degrees C. ONAs also display several attributes in common with the naturally occurring DNA. For example, oT15 exhibited cross-pairing with complementary RNA to give a duplex (oT15/rA15) whose conformation evaluated by CD spectroscopy very closely matched that of the natural DNA/RNA hybrid (dT15/rA15). Furthermore, oT15 was found to elicit Escherichia coli RNase H-mediated degradation of the rA15 strand. When we compared the rates of RNase H-mediated degradation induced by 5- (furanose, dT15), 6- (2'-enopyranose, pT18), and 7-membered (oxepane, oT15) ring oligonucleotides at a temperature that ensures maximum duplex population (10 degrees C), the following trend was observed: dT15 >> oT15 > pT18. The wider implications of these results are discussed in the context of our current understanding of the catalytic mechanism of the enzyme. The homopolymer oT15 also paired with its oxepane complement, oA15, to form a duplex structure that was different [as assessed by circular dichroic (CD) spectroscopy] and of lower thermal stability relative to the native dT15/dA15 hybrid. Hence, ONAs are useful tools for biological studies and provide new insights into the structure and function of natural and alternative genetic systems.
authors.affiliation: Contribution from the Department of Chemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Sabatino
authors.forename: Masad J
authors.initials: MJ
authors.lastname: Damha
mesh_terms: D002236:Carbohydrate Conformation; D002241:Carbohydrates / Q000737:chemistry*; D002942:Circular Dichroism; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry* / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry* / Q000378:metabolism; D012260:Ribonucleases; D013696:Temperature
chemical_list: D002241:Carbohydrates; D009696:Nucleic Acids; D009841:Oligonucleotides; D012260:Ribonucleases