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Nucleic Acids Symposium Series 2001 1(1):57-58; doi:10.1093/nass/1.1.57
© 2001 by Oxford University Press
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Promotion of triplex formation by N3'->P5' phosphoramidate modification: Thermodynamic and kinetic studies

Hidetaka Torigoe

The Institute of Physical and Chemical Research (RIKEN), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan

I examined the effect of N3'->P5' phosphoramidate (PN) backbone modification of triplex-forming oligonucleotide (TFO) on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. Both thermodynamic and kinetic analyses have indicated that the PN modification of TFO increased the binding constant of the pyrimidine motif triplex formation at pH 6.8 by nearly 2 orders of magnitude. Kinetic data have also demonstrated that the observed increase in the binding constant at neutral pH by the PN modification resulted mainly from the considerable decrease in the dissociation rate constant rather than the increase in the association rate constant. The present results certainly support the idea that the PN modification of TFO could be a key modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.


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