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Asako Yamayoshi

Publications and source records attributed to Asako Yamayoshi.

8 recordsLinked to original sources

Cationic comb-type copolymers for boosting DNA-fueled nanomachines.

For the better applications and developments of DNA nanomachines, their responding kinetics, output, and sequence-selectivity need to be improved. Furthermore, the DNA nanomachines currently have several limitations in operating conditions. Here we show that a simple addition of a cationic comb-type copolymer, poly(l-lysine)-graft-dextran, produces the robust and quick responses of DNA nanomachines under moderate conditions including physiologically relevant conditions even at very low strand concentrations (nanomoles per liter range) through hybrid stabilization and DNA strand exchange acceleration.

Base Sequence↗

Structural effect of cationic copolymers on nucleic acid-chaperoning activity.

In order to evaluate the effect of cationic copolymer structures on their nucleic acid-chaperoning activity, we prepared various copolymers having different cationic residues or backbone molecular weight. It was revealed that nucleic acid-chaperoning activity increases with increasing molecular weight of the copolymer backbone and that the copolymer having the guanidino groups is effective for increasing nucleic acid-chaperoning activity. Compared with PLL-g-Dex, GPLL-g-Dex has weak activity to stabilize ds DNA. This weak stabilization effect of GPLL-g-Dex may contribute to the higher accelerating effect.

DNA↗

Single-base mismatch recognition using partially double-stranded probes having various lengths.

We have focused on the nucleation-synchronized DNA strand exchange reaction (ns-SER) as a format of a single-base mismatch detection. We employed a partially double-stranded (PDS) DNA probe having a single-stranded (ss) portion. We could rapidly resolve a single-base mismatch by the ns-SER rates of the PDS probe with target DNAs. Here, we reported the influence of probe length and operating conditions, such as temperature and buffer conditions, on a single-base mismatch recognition using the PDS probes. We could reliably recognize a single-base mismatch even with a 61mer long probe. However, the ns-SER rates were decreased with increasing probe length. We considered that a rate-limiting step of the ns-SER might be sifted from nucleation to branch migration processes. By an addition of cationic comb-type copolymers (PLL-g-Dex) in the buffer, the reaction rate was considerably increased 1-2 orders without disordering the resolution power.

Base Pair Mismatch↗

Discrimination of single nucleotide polymorphisms by strand exchange assay using partially double-stranded probes.

Previously we designed the partially double-stranded (PDS) probes that have protruding single-stranded portion for a single-base mismatch analysis. The single-stranded portion is engineered to sense existences of mismatches in the counterparts and to transduce it in strand exchange rates. Here we report the influence of probe length and operating conditions, such as temperature and buffer conditions, on the mismatch resolution using the PDS probes. Reliable detection of single-base mismatches was achieved even with a 45mer-long probe. By lowering operating temperature, the higher and faster discrimination of the mismatches was demonstrated. Addition of cationic comb-type copolymers (CCCs) in the buffer increased the reaction rate 3-4 orders without disordering the resolving power.

Base Pair Mismatch↗

Synthesis and properties of photo-reactive antisense oligonucleotides containing 2'-O-psoralen-conjugated adenosine.

In order to selectively regulate mRNA having a point mutation, the photo-reactive antisense oligonucleotides were developed. Two types of photo-reactive oligonucleotides containing adenosine whose 2'-OH was modified with 4,5',8-trimethylpsoralen (psoralen) were synthesized (2'-Ps-oligo). One contains psoralen via a methylene linkage (2'-Ps-met), and the other via an amidomethylene linkage (2'-Ps-amd). 2'-Ps-oligos were then subjected to the photo-cross-linking reaction. 2'-Ps-met cross-linked to the complementary RNA and scarcely did to the RNA having a single mismatch base. Contrarily, 2'-Ps-amd did not cross-link to both RNA strands. These results suggest the structure of the linkage might affect the efficiency of the photo-cross-linking.

Adenosine↗

Modulation of highly ordered structures of human telomeric sequence by cationic copolymers.

Human telomeric DNA, d(GGGTTA)n, tends to adopt complex intramolecular G-quadruplex structure in solution. The sequence folds into G-quadruplex with the antiparallel orientation in the presence of sodium ions, while antiparallel and parallel conformations were coexisted in solution containing relatively high concentration of potassium ions. Here, we describe that cationic comb-type copolymer, poly(l-lysine)-graft-dextran (PLL-g-Dex), triggers selective folding of d[GGG(TTAGGG)3] into G-quadruplex with the parallel orientation. The parallel G-quadruplex formed in the presence of the copolymer has the melting temperature > 90 degrees C, including strong stabilization effect of the copolymer.

Base Sequence↗

Photodynamic antisense therapy: regulation of cervical carcinoma cells by psoralen-conjugated oligonucleotides.

To reinforce antisense effects, we focused on the photo-cross-linking ability of psoralen derivatives and examined the applicability of the photodynamic antisense therapy to cancer cells using psoralen-conjugated oligo(nucleosides phosphorothioate)s (Ps-S-Oligo). The regulatory effects of Ps-S-Oligos on the proliferation of cervical carcinoma were evaluated. The inhibitory effects were found to be significant (IC50=16 nM) without any drug delivery systems, and it was also found that the mechanism was associated with the p53 induced apoptosis. This result suggests that the photodynamic antisense therapy will be a promising concept for the cancer therapy.

Apoptosis↗