Kinetic analyses and structure-activity relationship studies of synthetic lysine acetylation catalysts

Kenzo Yamatsugu, Masahiro Furuta, Siqi Xi, Yoshifumi Amamoto, Jiaan Liu, Shigehiro A. Kawashima, Motomu Kanai

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Lysine acylation of proteins is a crucial chemical reaction, both as a post-translational modification and as a method for bioconjugation. We previously developed a chemical catalyst, DSH, which activates a chemically stable thioester including acyl-CoA, allowing the site-selective lysine acylation of histones under physiological conditions. However, a more active catalyst is required for efficient lysine acylation in more complex biological milieu, such as in living cells, but there are no rational guidelines for developing efficient lysine acylation catalysts for use under physiological conditions as opposed to in organic solvents. We, herein, conducted a kinetic analysis of the ability of DSH and several derivatives to mediate lysine acetylation to better understand the structural elements essential for high acetylation activity under physiological conditions. Interestingly, the obtained trend in reactivity was different from that observed in organic solvents, suggesting that a different principle is necessary for designing chemical catalysts specifically for use under physiological conditions compared to catalysts for use in organic solvents. Based on the obtained information, we identified a new catalyst scaffold with high activity and structural flexibility for further modification to improve this catalyst system.

元の言語英語
ページ(範囲)5359-5367
ページ数9
ジャーナルBioorganic and Medicinal Chemistry
DOI
出版物ステータス出版済み - 10 15 2018

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Acetylation
Structure-Activity Relationship
Acylation
Lysine
Catalysts
Kinetics
Organic solvents
Acyl Coenzyme A
Post Translational Protein Processing
Histones
Guidelines
Scaffolds
Chemical reactions
Cells
Derivatives
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

これを引用

Kinetic analyses and structure-activity relationship studies of synthetic lysine acetylation catalysts. / Yamatsugu, Kenzo; Furuta, Masahiro; Xi, Siqi; Amamoto, Yoshifumi; Liu, Jiaan; Kawashima, Shigehiro A.; Kanai, Motomu.

:: Bioorganic and Medicinal Chemistry, 15.10.2018, p. 5359-5367.

研究成果: ジャーナルへの寄稿記事

Yamatsugu, Kenzo ; Furuta, Masahiro ; Xi, Siqi ; Amamoto, Yoshifumi ; Liu, Jiaan ; Kawashima, Shigehiro A. ; Kanai, Motomu. / Kinetic analyses and structure-activity relationship studies of synthetic lysine acetylation catalysts. :: Bioorganic and Medicinal Chemistry. 2018 ; pp. 5359-5367.
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abstract = "Lysine acylation of proteins is a crucial chemical reaction, both as a post-translational modification and as a method for bioconjugation. We previously developed a chemical catalyst, DSH, which activates a chemically stable thioester including acyl-CoA, allowing the site-selective lysine acylation of histones under physiological conditions. However, a more active catalyst is required for efficient lysine acylation in more complex biological milieu, such as in living cells, but there are no rational guidelines for developing efficient lysine acylation catalysts for use under physiological conditions as opposed to in organic solvents. We, herein, conducted a kinetic analysis of the ability of DSH and several derivatives to mediate lysine acetylation to better understand the structural elements essential for high acetylation activity under physiological conditions. Interestingly, the obtained trend in reactivity was different from that observed in organic solvents, suggesting that a different principle is necessary for designing chemical catalysts specifically for use under physiological conditions compared to catalysts for use in organic solvents. Based on the obtained information, we identified a new catalyst scaffold with high activity and structural flexibility for further modification to improve this catalyst system.",
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AU - Xi, Siqi

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AU - Liu, Jiaan

AU - Kawashima, Shigehiro A.

AU - Kanai, Motomu

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