Biology subjects

Homma, T.

Publications and source records attributed to Homma, T..

3 recordsLinked to original sources

bioRxiv2025

Identification of KKL-35 as a novel carnosine dipeptidase 2 (CNDP2) inhibitor by in silico screening

Extracellular glutathione (GSH) is degraded on the cell surface, in which the {gamma}-glutamyl residue is removed to generate cysteine-glycine (Cys-Gly) dipeptides that are subsequently transported to the cytoplasm. Carnosine dipeptidase II (CNDP2) is a cytoplasmic enzyme that hydrolyzes Cys-Gly and plays an important role in maintaining intracellular cysteine (Cys) homeostasis. CNDP2-mediated hydrolysis of Cys-Gly promotes Cys mobilization and contributes to the replenishment of intracellular GSH levels. CNDP2 is frequently overexpressed in various cancers and has been implicated in tumor cell proliferation and progression. This mechanism may enhance cancer cell survival by causing resistance to oxidative stress, which indicates that CNDP2 is a potential therapeutic target for cancer treatment. Although bestatin (BES) has been identified as a CNDP2 inhibitor, its limited specificity and suboptimal drug-like properties have limited its therapeutic potential. In this study, we performed an in silico screen of a small-molecule compound library and identified KKL-35 as a novel CNDP2-binding molecule. Molecular dynamics (MD) simulations suggested that KKL-35 interacts within the catalytic pocket. Biochemical assays confirmed that it inhibits CNDP2 enzymatic activity, albeit with lower potency compared with BES. Despite its modest intrinsic activity, KKL-35 exhibits favorable physicochemical and pharmacokinetic properties, which are characterized by a low topological polar surface area (TPSA), reduced molecular flexibility, and well-balanced lipophilicity. This positions it as an attractive and tractable starting point for lead optimization. Taken together, these findings establish KKL-35 as a validated CNDP2 inhibitor and a promising lead compound for the development of more selective therapeutics targeting CNDP2-mediated cancer cell metabolism.

bioinformatics↗

bioRxiv2025

Self/non-self discrimination in tendrils of the vine Cayratia japonica with electrical signals

Recent studies have shown that the vine Cayratia japonica (C. japonica) has a self/non-self discrimination ability via its tendrils. However, the mechanism of self/non-self discrimination in tendrils of C. japonica remains unclear. Here, we show that tendrils of C. japonica discriminated between self and non-self plants with electrical signals generated by the contact of tendrils. We conducted touch experiments with C. japonica and detected electrical signals generated by the contact of tendrils. We found that when the tendril contacted the stem and did not coil around it, the electrical signal was transmitted from the stem to the tendril. On the other hand, when the tendril coiled around the stem, no electrical signal was transmitted. These results suggest that the electrical signals inhibited the coiling of tendrils, and the following experiment was conducted to verify this hypothesis: (1) when the tendrils did not coil around the stems after contacting the stems, the tendrils were removed from the stems and contacted a stick to coil around it. (2) Contact stimuli were applied to the part of the stems where the tendrils did not coil around, and the tendril uncoiled. We found that self/non-self discrimination was realised by electrical signals that inhibited coiling generated by contact stimuli.

plant biology↗

bioRxiv2024

A Novel Gene Synthesis Platform for Designing Functional Protein Polymers

Recombinant protein polymers with repeat sequences of specific amino acids can be regarded as sustainable functional materials that can be designed using genetic engineering. However, synthesizing genes encoding these proteins is significantly time-consuming and labor-intensive owing to the difficulty of using common gene synthesis tools, such as restriction enzymes and PCR primers. To overcome these obstacles, we propose a novel method: seamless cloning of rolling-circle amplicons (SCRCA). This method involves one-pot preparation of repetitive-sequence genes with overlapping ends for cloning, facilitating the easy construction of the desired recombinants. Using SCRCA, we synthesized 10 genes encoding hydrophilic resilin-like and hydrophobic elastin-like repeat units that induce liquid-liquid phase separation. SCRCA shows higher transformation efficiency and better workability than conventional methods, and the time and budget required for SCRCA are comparable to those required for non-repetitive-sequence gene synthesis. Additionally, SCRCA allows the construction of a repeat unit library at a low cost. The library shows considerably higher diversity compared with that of the state-of-the-art method. By combining this library construction with the directed evolution concept, we can rapidly develop an elastin-like protein polymer with a desired function. SCRCA can greatly accelerate research on protein polymers.

bioengineering↗