Tohoku University · Biochemistry, Genetics and Molecular Biology
Professor Hirokazu Arimoto's research lab specializes in innovative drug discovery strategies, with a focus on targeted protein degradation and the development of novel antibiotics. The lab pioneers the design of autophagy-based degraders (AUTACs) that exploit cysteine modification to selectively degrade disease-related proteins, offering a promising approach to target the 'undruggable' proteome. Additionally, the lab develops advanced synthetic methodologies for complex natural products and antibacterial agents, such as multivalent vancomycin derivatives, to combat drug-resistant pathogens.
Figures are computed from collected data and may differ slightly.
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.
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