Several Results in the Lab

New hybridization probes based on excitonic interaction for DNA/RNA imaging

Aggregation of thiazole orange dyes tethered to a single nucleotide in DNA dramatically changes the photophysical properties of the dyes, as demonstrated by the large spectral shifts relative to the absorption of the monomeric dyes intercalating into DNA. The photophysically designed DNA showed strong emission when it hybridized with the target strand, whereas the emission was suppressed strongly in the single-stranded state. The present approach using an excitonic interaction exhibits a quenching ability that is high enough to work as an on–off probe for live-cell RNA imaging assays.

Development of conceptually new epigenotyping method using organic chemistry

The development of a reaction for the detection of the presence/absence of one epigenetic modification in a long DNA strand is a chemically and biologically challenging research subject. Several newly designed chemical assays for the detection of DNA methylation or hydroxymethylation have been developed. A new concept of sequence-specific short-term methylation analysis, supported by a chemical basis, is the starting point for a novel epigenotyping assay, which will supersede conventional methods.

Chemical modification toward creation of functional proteins/oligopeptides

An artificial phosphopeptide has been developed through rational design of the interaction with 5-methylcytosine in duplex DNA. The peptide consists of two tandem zinc finger motifs, in one of which the glutamate was replaced with a phosphotyrosine, the phosphotyrosine in the peptide being effective for methylcytosine selectivity of DNA binding by maintenance of binding ability with methylated cytosine and a large decrease in binding ability with unmethylated cytosine. The flexible modulation of the target methylated sequence by rearrangement of zinc finger peptides is possible, and the phosphopeptide provided us an important hint for expansion of the codes for the interactions of zinc fingers with DNA to methylated DNA sequences.

 

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