Tohoku University · 생화학·유전·분자생물학
히로카즈 아리모토 교수의 연구실은 항생제 내성 세균에 효과적인 다가성 항생제 개발과 타겟팅 단백질 분해 기술을 핵심으로 하는 약물 개발 분야에서 활발한 연구를 수행하고 있습니다. 특히 범용성 항생제인 밴코마이신의 다중 결합체를 통해 내성 세균에 대한 항균 활성을 극대화하고, 자가분해 작용을 이용한 새로운 단백질 분해 기법인 AUTACs를 개발하여 '불가약한 단백질'까지 표적으로 삼을 수 있는 가능성을 열어가고 있습니다. 또한 자연물 합성과 촉매 반응을 활용한 고차원적 구조 합성 기법 개발을 통해 생활물질의 합성 및 기능화에 기여하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
A multivalent polymer of vancomycin, synthesized via ring-opening metathesis polymerization (ROMP), exhibited significant enhancement of antibacterial activity against vancomycin-resistant enterococi (VRE).
Targeted degradation is a promising new modality in drug discovery that makes it possible to reduce intracellular protein levels with small molecules. It is a complementary approach to the conventional protein knockdown typically used in laboratories and may offer a way to approach the currently undruggable human proteome. Recently, the first autophagy-mediated degraders, called AUTACs, were developed based on observations in a xenophagy study.
The enantioselective total synthesis of the bioactive marine natural products pinnaic acid and halichlorine is reported in detail. Our total synthesis features the construction of the five-membered ring and C9 and C13 stereogenic centers through a palladium-catalyzed trimethylenemethane [3+2] cyclization; the installation of the nitrogen atom through a regioselective Beckmann rearrangement of a poorly reactive ketone; the stereoselective cyclization of the spiro ring through a four-step, one-pot
Targeted protein degradation via the ubiquitin-proteasome system has emerged as one of the most promising drug discovery modalities. Autophagy, another intracellular degradation system, can target a wide range of nonproteinous substrates as well as proteins, but its application to targeted degradation is still in its infancy. Our previous work revealed a relationship between guanine modification of cysteine residues on intracellular proteins and selective autophagy, resulting in the first autoph
±)-Pinnaic acid (1) was synthesized via the catalytic hydrogenation of an α, β-unsaturated ketone (12) as the key step to construct
A novel and efficient avenue for the preparation of dimeric vancomycins is described, and the dimers exhibited excellent antibacterial activities in the murine infection model.
