Junlin He

8-Aza-7-deazapurine–pyrimidine base pairs: the contribution of 2- and 7-substituents to the stability of duplex DNA

Abstract The 8-aza-7-deazapurin-2,6-diamine 2′-deoxyribonucleoside ( 2a )–dT base pair is more stable than the 2-amino-2′-deoxyadenosine ( 1 )–dT pair. Halogeno or propynyl substituents introduced in the 7-position of the 8-aza-7-deazapurine system ( 2b–d ) lead to an additional duplex stabilization. Pyrazolo[3,4-d]pyrimidine nucleosides related to 2′-deoxyadenosine or 2′-deoxyguanosine show a similar behavior. The base pair stabilization is comparably small when identical substituents are present in the 5-position of 2′-deoxyuridine. The extraordinary stability of the 2b–d –dT base pairs is caused by better proton donor properties of the two amino groups of the 8-aza-7-deazapurin-2,6-diamine moiety and the better base stacking induced by the 7-substituents compared to that of 2-aminoadenine.

Base-Modified Oligonucleotides With Increased Duplex Stability

: Oligonucleotides incorporating 8-aza-7-dazapurines (pyrazolo[3,4-d]pyrimidines) were synthesized. The corresponding nucleosides were prepared and were converted into phosphoramidites. The oligonucleotide duplex stability was studied and was compared to that of the parent compounds containing the canonical purine nucleosides. The presence of 7-halogeno or 7-alkynyl substituents increases the duplex stability significantly.

Comparative conformational analysis of nucleosides by NMR, X-ray, and semi-empirical (PM3 VS. AM1) methods.

The 2′-deoxy-2′-fluoro-β-D-arabinofuranosyl ortho-aza-purine and -pyrimidine nucleosides manifest an unusually rigid sugar N conformation in solution.

6-azapyrimidine and 7-deazapurine 2'-deoxy-2'-fluoroarabinonucleosides : Synthesis, conformation and properties of oligonucleotides

The synthesis of 2′-deoxy-2′-fluoro-β-d-arabinofuranosyl nucleosides (1b, 2b, and 3b) were described and their conformation in solution as well as in the solid state was determined. In addition to this, building blocks 10a,b and 13a,b were prepared and employed in solid-phase oligonucleotide synthesis. For compounds 1a and 1b the lactime proton is protected to avoid unresolved degradation of its phosphoramidites 10a,b. UV-melting studies have been carried out to assess the thermal stability of oligonucleotides containing compounds 1a,b, and 3a,b.

3-Bromo-1-(2-deoxy-β-d-erythro-pento­furan­osyl)-1H-pyrazolo­[3,4-d]­pyrimidine-4,6-di­amine: a nucleoside which strongly enhances DNA duplex stability

The title compound, C10H13BrN6O3, exhibits an anti glycosylic bond conformation, with an O-C-N-C torsion angle of -105.0 (6) degrees . The pseudorotation phase angle and the amplitude [P = 5.8 (5) degrees and tau(m) = 30.0 (3) degrees , respectively] indicate N-type sugar puckering (3T2).

Pyrazolo[3,4-d]pyrimidine nucleic acids: adjustment of the dA-dT to the dG-dC base pair stability.

Abstract The pyrazolo[3,4-d]pyrimidine-4,6-diamine nucleosides 2b-d stabilize the dA-dT base pair significantly when the dA-residue is replaced. Oligonucleotide duplexes incorporating 2b-d show a 4–6°C T m increase per modification. The 7-bromo compound 2b harmonizes the stability of the dA-dT vs. the dG-dC pair. According to this the stability of such duplexes depends no longer on the base pair composition of a DNA molecule.