International Journal of Molecular Sciences | |
Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study | |
Ohgi Takahashi1  Ryota Kirikoshi2  Noriyoshi Manabe2  | |
[1] Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan; | |
关键词: aspartic acid residue; nonenzymatic reaction; succinimide; density functional theory; computational chemistry; acetic acid; buffer catalysis; double proton transfer; concerted bond reorganization; protein drugs; | |
DOI : 10.3390/ijms16011613 | |
来源: mdpi | |
【 摘 要 】
Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a
【 授权许可】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
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