Conversion of Commercial Peptides into “Clickable” Derivatives for Labeling and Conjugate Synthesis

Peptides conjugated to labels as well as to other biomolecules are essential tools in biomedical research.1,2 We have developed a convenient method for conversion of commercially available basic peptides into protected derivatives that can be readily used in synthesis of conjugates between the peptide and different labels/signals or other biomolecules. To achieve this we have converted the peptides into alkyne and azide derivatives at the carboxyterminus so that the peptide can be further reacted in a site selective fashion by 1,3-dipolar cycloaddition chemistry (click chemistry). 3,4 The method involves protection of aminofunctions in the peptide as trifluoroacetamides followed by coupling to either propargylamine or azidoethylamine. The protection can then be kept or optionally removed before use in subsequent click reactions.