AMINO ACID DERIVATIVE DESIGN USING COMPUTATIONAL CHEMISTRY AND APPLICATION TO PET TRACER

This study investigated positron emission tomography (PET) agents, which can be bind to Glutamate Transporter (GLT) from amino acid structures. The original amino acids passes through the transporter. Alternatively, focusing only on binding to GLT from the calculation results, the permeability of the blood-brain barrier (BBB) decreased. This study established the synthesis of the GLT imaging agent using an in silico binding assay and addressed the permeability of the BBB using lipid solubility and the molecular size of structural compounds.From the in silico binding assay, we derived the binding structure of GLT adding the conditions for BBB permeability and studied the labeling of PET tracers using 11C or 18F radioisotopes. Currently, this method can be applied to sequencing, label synthesis, and animal experiments.第57回ペプチド討論

Structural design of glutamate transporter 18F-PET agent and synthesis using a Click-Reaction

Background and purposeWe excelled off-target binding using computer chemistry techniques and worked on the development of PET imaging agents that bind to glutamate transporter (GLT). Although a plurality of asymmetric carbons generated within the compound skeleton could be excluded by structure optimization, there was a problem with deprotection of the aspartic acid skeleton in the skeleton. This study aims at establishing synthesis reactions that do not require protection / deprotection reaction by Click-Reaction, recalculation of In Silico binding assay, and synthesis of obtained structural compounds.MethodIn silico binding assay we derive the predominant and ERα non-binding structure in GLT binding and have studied labeling by [18F] on synthesis and synthesizer. In the structure reported earlier, there was a problem in deprotection of the aspartic acid skeleton in the skeleton. We examined the establishment of synthetic reactions that do not require protection / deprotection reaction by Click-Reaction.Results and discussionWe have established a design and synthesis route for compounds excluding asymmetric positions. However, as the yield in the deprotection reaction was low, a synthesis reaction that did not require protection / deprotection reaction by Click-Reaction was established. At present, the labeling reaction is preparing for sequencing at the time of synthesis, label synthesis, and animal experiments.The 2021 International Chemical Congress of Pacific Basin Societies (Pacifichem 2021

小児におけるベクロニウムの呼吸と末梢骨格筋に対する筋弛緩効果発現差の検討

雑誌掲載

非脱分極性筋弛緩効果残存時の中枢性片麻痺患者の健側と麻痺側の反応差

雑誌掲載版中枢性片麻痺27例に非脱分極性筋弛緩薬パンクロニウムを投与し,その後の筋弛緩回復過程に抗コリンエステラーゼ薬とテタヌス刺激を加え,それに伴う健側と筋麻痺側のtwitch responseの反応差につき検討した.抗コリンエステラーゼ薬による拮抗作用は筋弛緩薬投与後に認めたtrain-of-four ratio (TOFR)較差を有したまま,ほぼ逆の経過で発現した.筋弛緩効果残存時のテタヌス刺激後のpost-tetanic potentiationでのTOFRの増大程度は健側と麻痺側で有意差はなかっ

非脱分極性筋弛緩薬効果の筋麻痺側と健側との反応差

雑誌掲載版中枢性片麻痺31例に,非脱分極性筋弛緩薬パンクロニウムを投与し,健側と麻痺側のtrain of four ratio (TOFR)の反応差につき検討した.パンクロニウム投与後の健側と麻痺側のTOFR値の差が20%以上の17例(グループ1)とそれ以下の14例(グループ2)に大別した.麻痺が3週間以上経過例はグループ1, 3週間以内例の大部分はグループ2に属した.麻痺の性質は,28例が弛緩性で,両群にほぼ同等に含まれた.痙性は3例と少なかったが,全例グループ1に属した.筋力低下の程度と両側のTOFR値の差は相関しなかっ