A. M. Butlerov Chemistry Institute, Kazan Federal University, Kremlevskaya st. 18, 420008, Kazan, Russian Federation.
Amino Acids. 2020 May;52(5):811-821. doi: 10.1007/s00726-020-02854-z. Epub 2020 May 5.
The kinetics of oligopeptides formation in the flow systems glycine-sodium trimetaphosphate-imidazole/N-methylimidazole at thermocyclic regime has been investigated by HPLC and P NMR methods in the ranges of temperature from 45 to 90 °C and pH from 8.5 to 11.5. Detailed reaction mechanisms have been proposed and justified by quantum chemical calculations using DFT method at the CAM-B3LYP/TZVP level with accounting solvent effect by the C-PCM model. A new imidazole catalysis mechanism by which imidazole reacts with cyclic N,O-phosphoryl glycine giving N-imidazolyl-O-glycyl phosphate as a key intermediate was proposed and validated. It is emphasized that while in the absence of imidazoles, prebiotic activation of amino acids occurs at the N-terminus, in the presence of imidazoles it shifts to the O-terminus. This means that in the peptide elongation N-imidazolyl-O-aminoacyl phosphates play in prebiotic systems the outstanding role similar to that of aminoacyl adenylates formed at the ATP and aminoacyl-tRNA synthetases presence in biosystems. The new crucial role of imidazoles in prebiotic evolution has been noticed. The systems used and modes of their conversion can be good models for prebiotic peptide syntheses in a flow thermocyclic regime.
在热循环条件下，通过 HPLC 和 P NMR 方法研究了甘氨酸-三偏磷酸盐-咪唑/ N-甲基咪唑流动体系中寡肽形成的动力学。通过使用 DFT 方法在 CAM-B3LYP/TZVP 水平上进行量子化学计算，并通过 C-PCM 模型考虑溶剂效应，提出并验证了详细的反应机制。提出并验证了一种新的咪唑催化机制，其中咪唑与环状 N,O-磷酸甘氨酸反应，生成 N-咪唑基-O-甘氨酰磷酸盐作为关键中间体。强调的是，在没有咪唑的情况下，前生物氨基酸的活化发生在 N 末端，而在存在咪唑的情况下，它转移到 O 末端。这意味着在肽延伸中，N-咪唑基-O-氨基酸膦酸盐在前生物系统中发挥着与在生物系统中存在的 ATP 和氨基酸酰基-tRNA 合成酶形成的氨基酸酰基腺苷酸相似的突出作用。已经注意到咪唑在前生物进化中的新关键作用。所使用的系统及其转化模式可以作为热循环流动条件下前生物肽合成的良好模型。
