Carboxylic-Acid Labeling of Unprotected Peptides through Fischer Esterification

In spite of the rapid growth of the field of bioconjugation, chemoselective labeling of carboxylates in polypeptides is still difficult because of synthetic challenges and safety concerns of labeling reagents. In this Letter, we present structure-reactivity relationship study of alcohols for Fischer esterification on peptide substrates for facile chemical modification of carboxylic acid groups on peptide substrates.