What factors could have led to our modern amino acid alphabet?

Abstract

Although the myriad proteins found in all life are largely built from a set of 20 amino acids, many other amino acids exist in nature , and it remains a mystery why some were ultimately incorporated into proteins and others left out. In a new study investigating what could have driven this selectivity, researchers made peptides out of several sets of amino acids and compared their solubility and foldability—how readily they arranged themselves into protein-like structures ( J. Am. Chem. Soc. 2023, DOI: 10.1021/jacs.2c12987 ). The 20 canonical amino acids can be divided into early and late groups, according to when they were added to the amino acid alphabet. Starting from a core of seven early amino acids, Klára Hlouchová of Charles University, Stephen D. Fried of Johns Hopkins University, and coworkers added sets of other amino acids, made peptide libraries from each set, and compared them with peptides made