Biomedical subjects
Publications and source records attributed to Takuma Katayama.
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Ab initio calculations were carried out to characterize the structure and energetic of silver cation (Ag (I)) complex with cytosine (C:Ag:C) and mercury cation (Hg (II)) complex with thymine (T:Hg:T) systems. These metal-modified mismatch base pairs have been optimized using Hatree-Fock method without any symmetry constrains. Using above methods, the models of Ag (I) in a crosslink between O2 carbonyl oxygen of cytosine, O2(C):Ag:O2(C), and Hg (II) in a crosslink between N3 nitrogen atom of thymine, N3(T):Hg:N3(T) were obtained. Furthermore, the interaction energies of C:Ag:C and T:Hg:T models were estimated. The result showed that the coordination silver (I) cation with cytosine is more stable than hydrate state.
We examined the effect of the combination of the two triplex-stabilizing factors, poly(L-lysine)-graft-dextran (PLL-g-Dex) copolymer and 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) backbone modification of triplex-forming oligonucleotide (TFO), on the pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The combination of both stabilizing factors that was the triplex involving the 2',4'-BNA TFO in the presence of the copolymer synergistically increased the thermal stability of the pyrimidine motif triplex at neutral pH. The present results certainly support the idea that the combination of the stabilizing factors can be a key method for triplex stabilization and may lead to progress in therapeutic applications of the antigene strategy in vivo.
We analyzed the thermodynamics of purine motif triplex formations involving single mismatches of four different base triplets (A x A:T, T x A:T, A x T:A and T x T:A) by isothermal titration calorimetry. The T x A:T and A x A:T base triplets are the most stable and the A x T:A base triplet is the least stable among the four base triplets. The magnitude of the Gibbs free energy change varies within 1.0 kcal mol(-1) for the single mismatches of the base triplet. On the other hand, the magnitude of the enthalpy change exhibits very large sequence dependence with up to 14 kcal mol(-1) variation per the single mismatches among the four base triplets, which is 14 times larger than the sequence-dependent variation of the magnitude of the Gibbs free energy change. Thus, the single mismatches in the purine motif triplex do not have strong effects on the magnitude of the Gibbs free energy change, but the magnitude of the enthalpy change exhibits much larger sequence-dependent variations. The present results support the previously proposed nucleation-elongation mechanism of the triplex formation and offer some hints to design novel triplex-forming oligonucleotides with enhanced sequence specificity.