九州大学 · Biochemistry, Genetics and Molecular Biology
유호시노 교수의 연구실은 합성 고분자 나노입자를 활용한 '플라스틱 항체'(plastic antibodies) 및 '플라스틱 해독제'(plastic antidotes) 개발에 초점을 맞추고 있습니다. 특히 생체 내에서 목표 펩타이드 독소를 선택적으로 포획하고 중화하는 고분자 나노입자의 설계, 합성 및 기전 규명을 통해 천연 항체의 대체재를 개발하고자 합니다. 나노입자의 크기, 표면 전하, 수소화성 등 물리화학적 특성이 생체 내 성능에 미치는 영향을 체계적으로 분석하며, 생물학적 복잡한 환경에서도 기능하는 고성능 나노소재를 목표로 합니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
We report that simple, synthetic organic polymer nanoparticles (NPs) can capture and clear a target peptide toxin in the bloodstream of living mice. The protein-sized polymer nanoparticles, with a binding affinity and selectivity comparable to those of natural antibodies, were prepared by combining a functional monomer optimization strategy with molecular-imprinting nanoparticle synthesis. As a result of binding and removal of melittin by NPs in vivo, the mortality and peripheral toxic symptoms
A novel method for preparation of biomacromolecular imprinted nanoparticles is described. Combinations of functional monomers were polymerized in the presence of the imprinting peptide melittin in aqueous solution at room temperature to produce a small library of polymer nanoparticles. The template peptide and unreacted monomers are subsequently removed by dialysis. Nanoparticles (NPs) from the library were evaluated for their binding to melittin by 27 MHz QCM analysis. NPs prepared with optimiz
Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the c
Herein we report that an aqueous solution of temperature-responsive micro- and nanogel particles (GPs) consisting of N-isopropylacrylamide (NIPAm) and N-[3-(dimethylamino)propyl]methacrylamide (DMAPM) reversibly absorbs and desorbs CO(2) via a phase transition induced by cooling and heating cycles (30-75 °C). Below the phase-transition temperature, most of the amines in the swollen GPs are capable of forming ion pairs with absorbed bicarbonate ions. However, above the phase-transition temperatur
Thermoelectric conversion of low temperature, delocalized, and abundant thermal sources is crucial for the development of the Internet of Things (IoT) and/or a carbon-free society. Thermocells are of great interest in thermoelectric conversion of low-temperature heat due to the low cost and flexibility of components. However, significant improvement of the conversion efficiency is required for the practical use of the cells. Here, we report thermo-electrochemical cells driven by volume phase tra
Designed polymer nanoparticles (NPs) capable of binding and neutralizing a biomacromolecular toxin are prepared. A library of copolymer NPs is synthesized from combinations of functional monomers. The binding capacity and affinity of the NPs are individually analyzed. NPs with optimized composition are capable of neutralizing the toxin even in a complex biological milieu. It is anticipated that this strategy will be a starting point for the design of synthetic alternatives to antibodies.
We report that multifunctional polymer nanoparticles approximately the size of a large protein can be "purified", on the basis of peptide affinity just as antibodies, using an affinity chromatography strategy. The selection process takes advantage of the thermoresponsiveness of the nanoparticles allowing "catch and release" of the target peptide by adjusting the temperature. Purified particles show much stronger affinity (K(dapp) ≈ nM) and a narrower affinity distribution than the average of par
Plastic antibodies, synthetic polymer nanoparticles with antibody-like functions, have emerged as potential alternatives to protein antibodies. This paper focuses on recent developments of plastic antibodies for biomacromolecules and their application as antitoxins.
Hydrogel films composed of temperature-responsive microgel particles (GPs) containing amine groups work as stimuli-responsive carbon dioxide absorbent with a high capacity of approximately 1.7 mmol g(-1). Although the dried films did not show significant absorption, the reversible absorption capacity dramatically increased by adding a small amount of water (1 mL g(-1)). The absorption capacity was independent of the amount of added water beyond 1 mL g(-1), demonstrating that the GP films can rea
Although a number of procedures to create synthetic polymer nanoparticles (NPs) with an intrinsic affinity to target biomacromolecules have been published, little has been reported on strategies to control the binding kinetics of target recognition. Here, we report an enzyme-mimic strategy to control binding/dissociation rate constants of NPs, which bind proteins through multipoint interactions, by taking advantage of the temperature-responsive coil-globule phase transition of poly-N-isopropylac
Sepsis is a life-threatening condition caused by the extreme release of inflammatory mediators into the blood in response to infection (e.g., bacterial infection, COVID-19), resulting in the dysfunction of multiple organs. Currently, there is no direct treatment for sepsis. Here we report an abiotic hydrogel nanoparticle (HNP) as a potential therapeutic agent for late-stage sepsis. The HNP captures and neutralizes all variants of histones, a major inflammatory mediator released during sepsis. Th
Temperature-responsive nanogel particles with acids exhibiting large and reversible pK a shift are prepared by an ion-imprinting polymerization of stimuli responsive monomers, cross-linkers, and acidic monomers using protons as a template. The principles employed here should be broadly applicable to other stimuli-responsive materials and will be an integral step in the production of active proton transporter. As a service to our authors and readers, this journal provides supporting information s
Herein we revealed the design rationale of thermally responsive gel particle (GP) films that reversibly capture and release large amounts of CO<sub>2</sub> over a narrow temperature range (30-75 °C). The p<i>K</i><sub>a</sub> value of ammonium ions in the GPs at both the CO<sub>2</sub> capture temperature (30 °C) and release temperature (75 °C) is found to be the primary factor responsible for the stoichiometry of reversible CO<sub>2</sub> capture by the amines in the GP films. The p<i>K</i><sub
Effects of ultrasound irradiation on DNA polymerase (Klenow fragment, KF) reactions were studied on the template/primer DNA-immobilized quartz crystal microbalance (QCM). Under ultrasound irradiation, binding of KF to the DNA was suppressed due to the decrease of the binding rate constant (k(1)) and the increase of the dissociation rate constant (k(-)(1)). The catalytic elongation rate (k(cat)) was increased, but the stability of the KF/DNA/monomer ternary complex (K(m)) was decreased by the ult