Selection of turning-on fluorogenic probe as protein-specific detector obtained via the 10BASEd-T

In order to obtain a molecular probe for specific protein detection, we have synthesized fluorogenic probe library of vast diversity on bacteriophage T7 via the gp10 based-thioetherification (10BASEd−T). A remarkable turning-on probe which is excitable by widely applicable visible light was selected from the library

Selection of Color-Changing and Intensity-Increasing Fluorogenic Probe as Protein-Specific Indicator Obtained via the 10BASEd-T

To obtain a molecular probe for specific protein detection, we have synthesized fluorogenic probe library of vastdiversity on bacteriophage T7 via the gp10 based-thioetherificaion (10BASEd-T). A remarkable color-changing and turning-on probewas selected from the library, and its physicochemical properties upon target-specific binding were obtained. Combination analysesof fluorescence emission titration, isothermal titration calorimetry (ITC), and quantitative saturation-transfer difference (STD) NMRmeasurements followed by in silico docking simulation, rationalized most plausible geometry of the ligand-protein interaction

Medium-firm drug-candidate library of cryptand-like structures on T7: Design and selection of strong binder for Hsp90

We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 10^9 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (K_D = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD)

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研究論

Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

SARS-CoV-2オミクロンBA.2.75株（通称ケンタウロス）のウイルス学的性状の解明. 京都大学プレスリリース. 2022-10-12.The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5

Radial volumetric imaging breath-hold examination (VIBE) with k-space weighted image contrast (KWIC) for dynamic gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI of the liver: advantages over Cartesian VIBE in the arterial phase

To compare radial volumetric imaging breath-hold examination with k-space weighted image contrast reconstruction (r-VIBE-KWIC) to Cartesian VIBE (c-VIBE) in arterial phase dynamic gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (DCE-MRI) of the liver. We reviewed 53 consecutive DCE-MRI studies performed on a 3-T unit using c-VIBE and 53 consecutive cases performed using r-VIBE-KWIC with full-frame image subset (r-VIBEfull) and sub-frame image subsets (r-VIBEsub; temporal resolution, 2.5-3 s). All arterial phase images were scored by two readers on: (1) contrast-enhancement ratio (CER) in the abdominal aorta; (2) scan timing; (3) artefacts; (4) visualisation of the common, right, and left hepatic arteries. Mean abdominal aortic CERs for c-VIBE, r-VIBEfull, and r-VIBEsub were 3.2, 4.3 and 6.5, respectively. There were significant differences between each group (P < 0.0001). The mean score for c-VIBE was significantly lower than that for r-VIBEfull and r-VIBEsub in all factors except for visualisation of the common hepatic artery (P < 0.05). The mean score of all factors except for scan timing for r-VIBEsub was not significantly different from that for r-VIBEfull. Radial VIBE-KWIC provides higher image quality than c-VIBE, and r-VIBEsub features high temporal resolution without image degradation in arterial phase DCE-MRI. aEuro cent Radial VIBE-KWIC minimised artefact and produced high-quality and high-temporal-resolution images. aEuro cent Maximum abdominal aortic enhancement was observed on sub-frame images of r-VIBE-KWIC. aEuro cent Using r-VIBE-KWIC, optimal arterial phase images were obtained in over 90 %. aEuro cent Using r-VIBE-KWIC, visualisation of the hepatic arteries was improved. aEuro cent A two-reader study revealed r-VIBE-KWIC's advantages over Cartesian VIBE.ArticleEUROPEAN RADIOLOGY. 24(6):1290-1299 (2014)journal articl

Virological characteristics of the SARS-CoV-2 BA.2.86 variant

オミクロンBA.2.86株のウイルス学的特性の解明. 京都大学プレスリリース. 2024-01-30.A comprehensive systematic characterization of the SARS-CoV-2 strain BA.2.86. 京都大学プレスリリース. 2024-01-31.In late 2023, several SARS-CoV-2 XBB descendants, notably EG.5.1, were predominant worldwide. However, a distinct SARS-CoV-2 lineage, the BA.2.86 variant, also emerged. BA.2.86 is phylogenetically distinct from other Omicron sublineages, accumulating over 30 amino acid mutations in its spike protein. Here, we examined the virological characteristics of the BA.2.86 variant. Our epidemic dynamics modeling suggested that the relative reproduction number of BA.2.86 is significantly higher than that of EG.5.1. Additionally, four clinically available antivirals were effective against BA.2.86. Although the fusogenicity of BA.2.86 spike is similar to that of the parental BA.2 spike, the intrinsic pathogenicity of BA.2.86 in hamsters was significantly lower than that of BA.2. Since the growth kinetics of BA.2.86 are significantly lower than those of BA.2 both in vitro and in vivo, the attenuated pathogenicity of BA.2.86 is likely due to its decreased replication capacity. These findings uncover the features of BA.2.86, providing insights for control and treatment