1. (Aminomethyl)phosphonate derivatives of oligonucleotides.
- Author
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Fathi R, Huang Q, Syi JL, Delaney W, and Cook AF
- Subjects
- Base Sequence, Chemical Phenomena, Chemistry, Physical, Drug Stability, Models, Molecular, Molecular Sequence Data, Nucleic Acid Hybridization, Oligonucleotides chemistry, Organophosphorus Compounds chemistry, Oxygen chemistry, Phosphorus chemistry, Sensitivity and Specificity, Solutions, Structure-Activity Relationship, Oligonucleotides chemical synthesis, Organophosphorus Compounds chemical synthesis
- Abstract
Oligothymidylate (aminomethyl)phosphonates have been prepared, and their enzymatic and physicochemical properties have been studied. The individual isomers of the protected dimers have been separated, characterized, and incorporated into oligonucleotides in which the backbone consists of alternating (aminomethyl)phosphonate and phosphodiester linkages. One of these net neutral, single isomer oligonucleotides forms a duplex with its complementary sequence which is more stable than the corresponding natural counterpart, whereas the other isomer is considerably less stable. Specificity of hybridization is maintained, as determined by the reduction in melting temperature observed upon the introduction of mismatches into the complementary strand of the duplex. The (aminomethyl)-phosphonate linkage is stable toward enzymatic degradation but can be hydrolyzed in aqueous solution at elevated temperature.
- Published
- 1994
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