Novel DNA Analogues with 2-, 3- and 4-Pyridylphosphonate Internucleotide Bonds: Synthesis and Hybridisation Properties
2003 (English)In: New Journal of Chemistry, ISSN 1144-0546, Vol. 27, no 12, 1698-1705 p.Article in journal (Refereed) Published
Oligothymidylates modified with stereodefined 2-pyridyl-, 3-pyridyl- and 4-pyridylphosphonate moieties at one or two juxtaposed internucleotide positions were prepared, and their avidity towards complementary single stranded DNA and RNA, as well as toward double stranded DNA were evaluated by UV melting temperature and CD studies. It was found that the sense of chirality at the phosphorus centre and the position of the nitrogen atom in the pyridyl ring of a pyridylphosphonate moiety are important factors governing stability of double- and triple-stranded complexes formed by these oligonucleotides. DNA/DNA and DNA/RNA duplexes containing oligothymidylate strands with R-P-pyridylphosphonate units differed only slightly from unmodified reference complexes. In contrast to this, the S-P-pyridylphosphonate derivatives exhibited lower binding affinity than both their R-P-counterparts and the unmodified reference oligonucleotide T-20. Triplexes of oligo(thymidyl pyridylphosphonate)s with hairpin oligomer d(A(21)C(4)T(21)) were found mostly to be thermodynamically slightly more stable in pH 7.4 and less stable in pH 5.0 than non-modified complexes. As expected, oligonucleotides with pyridylphosphonate internucleotide bonds were recognised by 3'- and 5'-exonucleases but the chimeric oligonucleotide chains were not cleaved at the modi. cation sites.
Place, publisher, year, edition, pages
Royal Society of Chemistry , 2003. Vol. 27, no 12, 1698-1705 p.
IONIC OLIGONUCLEOSIDE METHYLPHOSPHONATES; MOLECULAR-DYNAMICS SIMULATION; HUMAN-IMMUNODEFICIENCY-VIRUS; H-PHOSPHONOTHIOATE DIESTERS; ANTISENSE OLIGONUCLEOTIDES; STEREOSPECIFIC OXIDATION; PHOSPHATE BACKBONE; MINOR-GROOVE; HUMAN PLASMA; B-DNA
Research subject Organic Chemistry
IdentifiersURN: urn:nbn:se:su:diva-23239DOI: 10.1039/b305689aOAI: oai:DiVA.org:su-23239DiVA: diva2:190874
Part of urn:nbn:se:su:diva-2022004-08-192004-08-192010-01-05Bibliographically approved