Zwitterionic Oligonucleotides

The fact that the 3,P-NMR signal of 183a can only be observed in pyridine-containing solution provides food for thought124). Viewed in conjugation with the idea that alkyl metaphosphates could form adducts such as 173 and 174 U9,120) as discussed above, formulation as a zwitterionic pyridine/metaphosphate adduct (188) seems reasonable. Similar adducts have also been found in the reaction of TPS with dinucleotides and trinucleoside diphosphate 126). In any case, the reactions of 183 or 188 are in full accord with the expected properties of a monomeric metaphosphate and its reactivity towards alcohols is far greater than that of all other reactive phosphorylation intermediates which can arise on reaction of TPS with oligonucleotides 126). 

Oligonucleotides with extended zwitterionic internucleotide linkages have been synthesised using two non-natural nucleosidic analogues, N-(2-hy-... 

Griffey, R.H. et al, 2 -0-aminopropyl ribonucleotides a zwitterionic modification that enhances the exonuclease resistance and biological activity of antisense oligonucleotides, /. Med. Chem., 39, 5100,1996. 

Panico, M., G. Sindona, and N. Uccella Bioorganic Applications of Mass Spectrometry. 3. Fast-Atom-Bombardment-Induced Zwitterionic Oligonucleotide Quasimolecular Ions Sequenced by MS/MS. J. Amer. Chem. Soc. 105, 5607 (1983). 

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