情報発信型人工タンパク質創製に向けた有機·生物有機化学的挑戦

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  • 大高 章
    徳島大学大学院ヘルスバイオサイエンス研究部

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タイトル別名
  • Development of Organic and Bio-organic Methodologies for the Synthesis of Proteins
  • 情報発信型人工タンパク質創製に向けた有機・生物有機化学的挑戦
  • ジョウホウ ハッシンガタ ジンコウ タンパクシツ ソウセイ ニ ムケタ ユウキ ・ セイブツ ユウキ カガクテキ チョウセン

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抄録

Functional analyses of endogenous proteins represent indispensable steps for development of drugs for the protein targets. Here, informative-function-incorporated artificial proteins corresponding to the targets should serve as a useful molecular device for evaluating the naturally occurring proteins as a potential drug target. Chemical synthesis and chemical manipulation of proteins allow such artificial proteins to be prepared. We therefore developed a facile synthetic protocol for proteins and a chemical device for functional change of proteins. In this review are addressed both N-sulfanylethylanilide (SEAlide) peptides for protein synthesis and stimulus-responsive amino acids for the functional conversion. SEAlide peptides were initially developed as peptide thioester precursors obtainable by 9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis. Investigation on the SEAlide peptides uncovered that a one-pot/multi-fragment sequential native chemical ligation (NCL) is achieved efficiently using the SEAlide unit to give proteins. For functional change of proteins, stimulus-responsive amino acids were developed. Upon responding to various stimuli, the newly developed amino acid-containing peptides are spliced into two peptide parts. Combination of the splicing reaction and an acyl-transfer chemistry allows the function of peptide to be changed.

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