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The microenvironment and pKa perturbation of aminoacyl-tRNA guided the selection of cationic amino acids
Organic & Biomolecular Chemistry ( IF 3.2 ) Pub Date : 2021-08-17 , DOI: 10.1039/d1ob00798j
Bibhas Hazra 1 , Mahesh Prasad 1 , Rajat Roy 1 , Pradip K Tarafdar 1
Affiliation  

The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and the terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino propionic acid (Dpr) with fewer methylene groups in the side chain remains an important question! The propensity of aminoacyl-tRNA (aa-tRNA) model substrates towards self-degradation via intramolecular lactamization was studied using UV spectroscopy and 1H-NMR titration, which showed that Lys and Arg remain stable, and Orn and Dab cyclize to lactam. Hydrophobicity-assisted surface mediated model peptide formation highlighted that the microenvironment and pKa perturbation led to poor regioselectivity (α-amine vs. terminal amine) in Dpr and other non-proteinogenic analogues. The α-selectivity became even poorer in the presence of phosphate, making them ill-suited for peptide synthesis. Superior regioselectivity of the Lys aa-tRNA model substrate suggests that the extra methylene bridge helped nature to separate the microenvironments of the α-amine and ε-amine to synthesize the peptide backbone.

中文翻译:

氨酰-tRNA的微环境和pKa扰动指导阳离子氨基酸的选择

蛋白质赖氨酸 (Lys) 和精氨酸 (Arg) 在 α-碳和末端带电中心之间具有多个亚甲基。为什么大自然没有选择侧链中亚甲基较少的鸟氨酸 (Orn)、2,4-二氨基丁酸 (Dab) 和 2,3-二氨基丙酸 (Dpr) 仍然是一个重要问题!使用紫外光谱和1 H-NMR 滴定法研究了氨酰-tRNA (aa-tRNA) 模型底物通过分子内内酰胺化自降解的倾向,结果表明 Lys 和 Arg 保持稳定,而 Orn 和 Dab 环化为内酰胺。疏水性辅助表面介导的模型肽形成强调了微环境和 p K a扰动导致区域选择性差(α-胺vs.末端胺)在 Dpr 和其他非蛋白原类似物中。在磷酸盐存在下,α-选择性变得更差,使其不适合肽合成。Lys aa-tRNA 模型底物的优越区域选择性表明,额外的亚甲基桥有助于自然界分离 α-胺和 ε-胺的微环境以合成肽骨架。
更新日期:2021-09-10
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