東京大学 · 生化学・遺伝学・分子生物学
Satoshi Yamaguchi教授の研究室は、生体分子の機能制御とその応用を柱とした分子工学的研究を展開しています。特に、タンパク質の効率的な精製・活性化、脂質ラフトの可視化、光・超音波応答型ドラッグデリバリーシステムの開発に注力しており、生命科学と材料科学の融合を実現しています。また、人工受容体とスーパーマルチスケールハイドロゲルの協働による分子認識デバイスの創出も重要な研究テーマです。
Figures are computed from collected data and may differ slightly.
In laboratories and manufacturing settings, a rapid and inexpensive method for the preparation of a target protein is crucial for promoting resesrach in protein science and engineering. Inclusion-body-based protein production is a promising method because high yields are achieved in the upstream process, although the refolding of solubilized, unfolded proteins in downstream processes often leads to significantly lower yields. The most challenging problem is that the effective condition for refol
This study has successfully demonstrated that the cooperative action of artificial receptors with semi-wet supramolecular hydrogels may produce a unique and efficient molecular recognition device not only for the simple sensing of phosphate derivatives, but also for discriminating among phosphate derivatives. We directly observed by confocal laser scanning microscopy that fluorescent artificial receptors can dynamically change the location between the aqueous cavity and the hydrophobic fibers up
Cells in the spotlight: A substrate was coated with a poly(ethylene glycol) (PEG) segment bound to a lipid through a linker that was cleaved by UV irradiation to leave a PEG-coated area. Irradiation of an arbitrary pattern easily and rapidly yielded a high-contrast cell pattern. Only the targeted cells on the cell pattern were selectively detached without cell damage on a microfluidic device (see picture). Detailed facts of importance to specialist readers are published as ”Supporting Informatio
A new method for site-specific caging of plasmid DNA was developed to enable light-activation of gene expression in living cells by exposure to a low dose of light.
An ultrasound‐responsive carrier for protein drugs is promising for site‐specific release of proteins at disease sites in a designated time course because ultrasound readily penetrates deep into the interior of the body in a non‐invasive way. However, the guideline for designing ultrasound‐responsive carriers that are applicable to any protein remains to be established. Here, the aim is to develop an ultrasound‐responsive material for the controlled release of a variety of proteins regardless of
The present study aimed to obtain more effective refolding agents and to understand the influence of their chemical structures on their function as refolding agents. To achieve these aims, we investigated the effects of a large variety of N'-substituted N-methylimidazolium chlorides on the oxidative refolding of lysozyme in a high throughput manner. Among the molecules examined, N-methylimidazolium cations with a short N'-alkyl chain, such as an N'-ethyl or N'-butyl chain, significantly enhanced
A chemically-activatable alkynyl steroid analogue probe has been synthesized for visualizing the lipid raft membrane domains by Raman microscopy. The Raman probe, in which ring A of its steroid backbone is replaced with an alkynyl group, was designed to enable activation of the alkyne signal through the Eschenmoser-Tanabe fragmentation reaction of the oxidized cholesterol precursor in lipid bilayer membranes. The alkynyl steroid analogue was observed to form liquid-ordered raft-like domains on a
Cell-surface display of functional proteins is a powerful and useful tool for regulating and reinforcing cellular functions. Direct incorporation of site-specifically lipidated proteins from the extracellular medium is more rapid, easily controllable and reliable in displaying active proteins than expression through gene transfer. However, undesirable amphiphilic reagents such as organic co-solvents and detergents were required for suppressing aggregation of ordinary lipidated proteins in soluti
The artificial regulation of protein functions is essential for the realization of protein-based soft devices, because of their unique functions conducted within a nano-sized molecular space. We report that self-assembled nanomeshes comprising heat-responsive supramolecular hydrogel fibers can control the rotary motion of an enzyme-based biomotor (F(1)-ATPase) in an on/off manner at the single-molecule level. Direct observation of the interaction of the supramolecular fibers with a microbead uni
Oxidative cyclization of <i>N</i>-acetyltryptamine by using iodobenzene diacetate (PIDA) provided the corresponding 1,2,3,3a,8,8a-hexahydropyrrolo[2,3-<i>b</i>]indol-3a-ol derivative, which could be derivatized following appropriate protection of the two amino and <i>tert</i>-hydroxyl groups. The facile one-pot procedure for cyclization and introduction of the oxygen functionality was applied in concise routes for the synthesis of the natural products CPC-1 and debromoflustraminol B.
Zellen im Scheinwerferlicht: Ein Substrat wurde mit einem Polyethylenglycol(PEG)-Segment bedeckt, das über einen Linker an ein Lipid gebunden war. Durch UV-Bestrahlung in beliebigen Mustern wurde der Linker gespalten, und eine PEG-bedeckte Fläche blieb zurück, sodass kontrastreiche Muster von Zellen einfach erhalten wurden, von denen selektiv die angestrahlten Zellen unbeschädigt in einem Mikrofluidikaufbau abgelöst werden können (siehe Bild).
A method for caging a target protein with steric regulator molecules was developed to enable simple, strict, light-induced control of protein activity.
G protein-coupled receptors (GPCRs) are important targets in medical and pharmaceutical research fields, because they play key roles in a variety of biological processes. Recently, intracellular trafficking of GPCRs involving endosomal internalization and recycling to the plasma membrane has been studied as a regulation mechanism for GPCR activities. However, the absence of a quantitative single-cell analysis method has hampered conditional GPCR trafficking studies and the possibility of gaining
Conformational changes of proteins immobilized on solid matrices were observed by measuring the adsorption of Triton X-100 (TX), a nonionic detergent, as a hydrophobic probe with BIACORE, a biosensor that utilizes the phenomenon of surface plasmon resonance (SPR). Two kinds of proteins, alpha-glucosidase and lysozyme, were covalently attached to dextran matrices on the sensor surface in the flow cell and then exposed to various concentrations of TX solution. We measured SPR signal changes derive
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