We designed synthetic substrates specific to target molecules to directly estimate enzymatic functionality in situ. It contains a probing unit, an organic fragment specific for enzyme-binding; and a reactive unit, a natural peptide subject to catalysis. In this study, activation of plasminogen to plasmin was examined in MDA-MB231 breast cancer cells, and the localization and function of plasmin were successfully visualized by fluorophore in the substrate. This would be the first time for activated plasmin at work in situ by direct observation.

The probes for specific detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to be useful for the identification, diagnosis, prevention, and treatment of atherosclerosis. We developed two fluorescein isothiocyanate (FITC)-labeled peptide compounds— (FITC)KP6 and (FITC-AC)KP6— bound with high specificity to ox-LDL in a dose-dependent manner. These compounds may be effective novel fluorescent probes for specific detection of ox-LDL.

Pair-wise randomly shuffled library was generated from once evolved peptides and subjected to selection providing nano-molar range affinity peptides to Aβ42 with the Aβ42 cytotoxicity inhibition activity.

Probes that can detection oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques can be useful for to the diagnosis, prevention, and treatment of atherosclerosis. We developed two fluorescence-labeled heptapeptides substituted with a D-amino acid— (FITC)dKP6 and (FITC-AC)dKP6— with high plasma stability for specific detection of ox-LDL. These compounds may be useful as fluorescent probes for specific detection of ox-LDL.

Seven analogs of μ-conotoxin GIIIA and two analogs of μ-conotoxin GIIIB were synthesized. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the side chain guanidino group of Arg¹³ of μ-conotoxin GIIIA was important for the activity, whereas that of Arg¹⁹ has little role in the biological activity. The results on the analogs of μ-conotoxin GIIIB suggested that there was an appropriate molecular basicity for the maximum activity.

By using the transition from cytosine of BFP gene to uridine of GFP gene at position 199 as a model, we successfully controlled photochemical RNA editing to effect site-directed deamination of cytidine to uridine. Western-blotting and fluorescence-analysis results revealed that the transition-GFP protein was synthesized from mRNAs after site-directed RNA editing.

Inhibitory effects of 17 bongkrekic acid analogues derived from the intermediates obtained during its total synthesis, on the mitochondrial ATP/ATP carrier were examined. One compound, KH-7, lacking one of the carboxylic groups of its parent compound, showed moderate but pH-intensive inhibitory effects on the mitochondrial ADP/ATP carrier.

To find compounds that restore splicing at the mutated acceptor site, we constructed a splicing reporter gene. Addition of a modified polypyrimidine tract to the reporter gene mediated splicing at adjacent non-canonical acceptor sites, including the original mutated site. Certain flavons such as luteolin and apigenin enhanced aberrant splicing at the original non-canonical acceptor site of the reporter gene.

We designed palmitic acid-conjugated Dicer-substrate 27-nt short interfering RNAs (C16-Dsi27RNAs) and investigated theirin vivo RNA interference effects in a subcutaneous tumor mouse model. C16-Dsi27RNAs had potent gene silencing activity against both enhanced green fluorescent protein and vascular endothelial growth factor as target genes in a subcutaneous tumor mouse model generated from GCIY-eGFP cells administered by intratumoral injection.

To optimize the ^CVU-containing-ODN structures, we investigated the dependence of the deamination efficiency on the effector ^CVU-containing ODN's complementary sequence length and hairpin loop length. We found that the deamination efficiency reached its maximum values with a complementary sequence length slightly more than 14 nt and hairpin loop length of 9 nt.

Alkylamine-modified sugars prepared via a microwave-assisted click reaction exhibited a unique relationship of their bacterial membrane permeabilization and antimicrobial activity with the number of functional groups and the size and shape of the molecular scaffold.

A series of compounds belonging to the purine scaffold have been screened for MTH1 inhibitory activity, and several new inhibitors with potency in the submicromolar range have been discovered. The structure activity relationship of these compounds has been analyzed, and their associated binding modes to MTH1 have been predicted using molecular docking. These studies have provided insights for the development of highly potent MTH1 inhibitors.