6-Aza-2‘-deoxyisocytidine:  Synthesis, Properties of Oligonucleotides, and Base-Pair Stability Adjustment of DNA with Parallel Strand Orientation

Abstract

6-Aza-5-methyl-2'-deoxyisocytidine (1a) and 6-aza-2'-deoxyisocytidine (1b) have been synthesized, converted into phosphoramidite building blocks, and incorporated into oligodeoxynucleotides. The glycosylic bond stability of 1a,b under acidic conditions increases compared to that of 5-methyl-2'-deoxyisocytidine (2a) and 2'-deoxyisocytidine (2b). Oligonucleotides incorporating 1a or 1b show an enhanced stability against the 3'-exonuclease snake-venom phosphodiesterase. The duplexes containing 6-azapyrimidine nucleosides 1a or 1b have lower T(m) values than duplexes containing 2a or 2b with either antiparallel or parallel chain orientation. This was used to adjust the stability of the tridentate m5iCd-dG base pair to the level of the bidentate reverse Watson-Crick dA-dT pair.

Complex self-assembly of pyrimido[4,5-d]pyrimidine nucleoside supramolecular structures

“…For the normal bidentate adenine–thymine base pairs, not only Watson–Crick but also reverse Watson–Crick pattern is possible, and the latter will lead to the formation of a parallel-stranded duplex DNA4647. The current J-AT system is endowed with the same options (Fig.…”

Metal–base pairing in DNA

“…Most interesting, however, turned out to be the modifications that were introduced right into the core of the DNA double helix, thus replacing the natural base pairs. Among these artificial nucleobases, some were developed for studying the hydrogen bonding and stacking forces that hold together the double helix [13]. Others were incorporated into DNA to create a new set of base pairs with pairing abilities orthogonal to the natural Watson-Crick base pairs [14].…”

Stabilizing or Destabilizing Oligodeoxynucleotide Duplexes Containing Single 2′‐Deoxyuridine Residues with 5‐Alkynyl Substituents

“…Probes rich in A and T form weak duplexes, which can cause false negative results in chip‐based experiments 7. Therefore, DNA chips with modified probes are beginning to emerge,8, 9 and efforts are being made to develop isostable DNA, that is, modified DNA where A:T and T:A base pairs are strengthened and/or G:C and C:G base pairs are weakened,10 such that the stability of the resulting DNA duplexes of a given length is independent of their sequence 11. For 2′‐deoxyadenosine residues in oligonucleotides, advances have been made toward analogues whose affinity for thymidine residues in DNA duplexes is similar to that of 2′‐deoxyguanosine for 2′‐deoxycytidine residues 12.…”