A prebiotic template-directed peptide synthesis based on amyloids.

Rout, Saroj K; Friedmann, Michael P; Riek, Roland; Greenwald, Jason · Nat Commun · 2018

basic_science · Level V

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Abstract

The prebiotic replication of information-coding molecules is a central problem concerning life's origins. Here, we report that amyloids composed of short peptides can direct the sequence-selective, regioselective and stereoselective condensation of amino acids. The addition of activated DL-arginine and DL-phenylalanine to the peptide RFRFR-NH<sub>2</sub> in the presence of the complementary template peptide Ac-FEFEFEFE-NH<sub>2</sub> yields the isotactic product FRFRFRFR-NH<sub>2</sub>, 1 of 64 possible triple addition products, under conditions in which the absence of template yields only single and double additions of mixed stereochemistry. The templating mechanism appears to be general in that a different amyloid formed by (Orn)V(Orn)V(Orn)V(Orn)V-NH<sub>2</sub> and Ac-VDVDVDVDV-NH<sub>2</sub> is regioselective and stereoselective for N-terminal, L-amino-acid addition while the ornithine-valine peptide alone yields predominantly sidechain condensation products with little stereoselectivity. Furthermore, the templating reaction is stable over a wide range of pH (5.6-8.6), salt concentration (0-4 M NaCl), and temperature (25-90 °C), making the amyloid an attractive model for a prebiotic peptide replicating system.

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