Formation of oligopeptides in high yield under simple programmable conditions

Abstract

Many high-yielding reactions for forming peptide bonds have been developed but these are complex, requiring activated amino-acid precursors and heterogeneous supports. Herein we demonstrate the programmable one-pot dehydration–hydration condensation of amino acids forming oligopeptide chains in around 50% yield. A digital recursive reactor system was developed to investigate this process, performing these reactions with control over parameters such as temperature, number of cycles, cycle duration, initial monomer concentration and initial pH. Glycine oligopeptides up to 20 amino acids long were formed with very high monomer-to-oligomer conversion, and the majority of these products comprised three amino acid residues or more. Having established the formation of glycine homo-oligopeptides, we then demonstrated the co-condensation of glycine with eight other amino acids (Ala, Asp, Glu, His, Lys, Pro, Thr and Val), incorporating a range of side-chain functionality.

A Possible Path to Prebiotic Peptides Involving Silica and Hydroxy Acid‐Mediated Amide Bond Formation

“…Consequently, researchers have long sought a plausible prebiotic reaction that would have condensed free AAs into peptides . However, the polycondensation of nonactivated AAs is thermodynamically unfavored in aqueous solution, and only proceeds in the dry state at elevated temperatures (e.g., 130 °C) or by vapor deposition on catalytic surfaces . In addition to the challenge of peptide bond formation, AA dimers have a strong propensity to cyclize, forming diketopiperazines, which greatly hinders the formation of longer peptides.…”

Matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry of model prebiotic peptides: Optimization of sample preparation

“…For the more hydrophobic a + V 8‐cycle sample, ACN was moderately effective when CHCA was used, yet it was still less effective than DHB. Previous analysis of pure glycine‐based peptides (not depsipeptides) in a prebiotic chemistry context also found DHB to be the best matrix …”

Stochastic Prebiotic Chemistry within Realistic Geological Systems

“…This setup was also able to demonstrate polymerization at temperatures of 200-250˚C, contrary to the popular belief that organic molecules are unstable under high temperatures. More recently, Cronin and colleagues [72] mimicked this hydrothermal system and developed an automated method to expose unactivated glycine monomers to prolonged dehydration-hydration cycles and, interestingly, chain lengths of 20 amino acid were observed. In addition to homo-oligomerization, the team was able to observe the heterooligomerization to chain lengths involving 8 different amino acids.…”