Understanding the diversity and chemical evolution of proto-peptides is of interest to origins-of-life research. Here, we have demonstrated MALDI-TOF mass spectrometry can be used to rapidly screen the length and monomer composition of model prebiotic peptides containing a mixture of ester and amide backbone linkages.

A one-pot method was developed for the preparation of a series of β-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of β-alanine methyl ester, yielding β-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of β-alanine peptide methyl ester oligomers, producing a series of β-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of β-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of β-peptide standards for investigating differences between α- and β-peptides in the context of prebiotic chemistry.

The cover image, by Sloane L. English and Jay G. Forsythe, is based on the Research Article MALDI‐TOF Mass Spectrometry of Model Prebiotic Peptides: Optimization of Sample Preparation, https://doi.org/10.1002/rcm.8201.