The microenvironment and pK_a perturbation of aminoacyl-tRNA guided the selection of cationic amino acids

Abstract

The proteinogenic lysine (Lys) and arginine (Arg) have multiple methylene groups between α-carbon and terminal charged centre. Why nature did not select ornithine (Orn), 2,4-diamino butyric acid (Dab) and 2,3-diamino...

Lipidated Lysine and Fatty Acids Assemble into Protocellular Membranes to Assist Regioselective Peptide Formation: Correlation to the Natural Selection of Lysine over Nonproteinogenic Lower Analogues

“…The possibility of Hbonding between the N−H of α-amine and the carbonyl of LysOct was suggested earlier. 44,54 In the presence of DA, the N−H of α-amine likely engaged in H-bonding with the carboxylate (COO − ), and therefore, the H-bonding probability to ester carbonyl may be reduced. The PXRD measurements of LysOct, DA, and LysOct−DA were carried out (Figure S28).…”

“…We have recently shown that a loosely packed micellar surface of LysOct can catalyze amide bond formation under physiological conditions. 44 We used the vesicular surface to carry out peptide formation at pH 7.0, 37 °C. Leucine phenolic ester (LP) was synthesized as a model aa-tRNA mimic and acylating agent to form peptide bonds with amines.…”

“…After ∼6 h, the white precipitate was filtered with Whatman 1 filter paper, washed with diethyl ether, and finally dried under vacuum to obtain the pure deprotected product as a white solid. The products were characterized by a JEOL 400 MHz 1 H NMR spectrometer and a Bruker Micro-TOF HRMS mass spectrometer …”

“…The products were characterized by a JEOL 400 MHz 1 H NMR spectrometer and a Bruker Micro-TOF HRMS mass spectrometer. 44 Reference Peptide Synthesis. We synthesized LysOct-α-Nleucine (terminal-amine-free) and LysOct-terminal-N-leucine (αamine-free) dipeptides following the conventional protection− deprotection strategy.…”

“…These nonproteinogenic analogues, Orn, Dab, and Dpr, have three, two, and one methylene units to connect the terminal ammonium group and α-carbon, respectively, whereas Lys has four methylene units. It is interesting to note that nature chose more expensive (more carbon atoms: four methylene) Lys over the other analogues. − Considering these facts, we ask whether lipidated Orn, Dab, and Dpr may also serve as model prebiotic cationic lipids to form protocellular membranes with fatty acids. In the present study, we have shown that a mixture of lipidated Lys and the fatty acid forms a catanionic-type complex and assembles into a protocellular membrane at a low concentration (Scheme ).…”