24630-57-7Relevant academic research and scientific papers
Hydroxymethylphosphonate: Novel oligonucleotide analogue
Lesnikowski
, p. 128 - 139 (1994)
Thymidine(3',5')thymidine hydroxymethylphosphonate (10), the first oligonucleotide bearing hydroxymethylphosphonate function, and t-butylammonium 5'-O-monomethoxytritylthymidine 3'-O-acetoxymethylphosphonate (7), oligonucleotide monomer, were synthesized using t-butylammonium O-methylacetoxymethylphosphonate (4) as a novel phosphonylating agent. Hydroxymethylphosphonate internucleotide linkage is stable at physiological pH and resistant to 3'- and 5'-exonucleases. While retaining the neutral character of the phosphonate modification, the presence of hydroxymethyl function increases hydrophilicity of hydroxymethylphosphonateoligonucleotide and its solubility in water compared to the parent methylphosphonate analogue. Therefore, hydroxymethylphosphonate modification can be used to fine-tune the physicochemical properties of antisense oligonucleotides.
Study on reactivity and protection of the α-hydroxyphosphonate moiety in 5′-nucleotide analogues: Formation of the 3′-O-P-C(OH)-C4′ internucleotide linkage
Kralikova, Sarka,Masojidkova, Milena,Budesinsky, Milos,Rosenberg, Ivan
, p. 329 - 347 (2007/10/03)
The recently described epimeric nucleosidyl-5′-C-phosphonates (α-hydroxyphos-phonates) represent novel nucleotide analogues that can be incorporated into chimeric oligonucleotides by the phosphotriester condensation method. In order to prepare suitable protected monomer(s) we have studied condensation reaction between protected 2′-deoxythymidine and 2′-deoxythymidinyl-5′-C-phosphonate, both as model compounds, in dependence on the nature of the 5′-hydroxyl protecting group. We have found that the O-acetyl group is unstable in the presence of TPSCl or MSNT used as condensing agents for activation of the phosphorus moiety. This instability negatively influences the scope of the condensation process. On the other hand, introduction of the O-methoxycarbonyl group gave excellent results. The O-methoxycarbonyl group does not participate in the condensation process, and its quantitative introduction into the nucleotide analogues is accomplished using a novel acylating agent, methoxycarbonyl tetrazole.
