Late-stage diversification of peptides provides access to larger arrays of modified peptides in the frame of a late synthetic step. Unlike modifications in an early stage of the synthesis, late-stage approaches allow for straightforward generation of a compound library, as one precursor molecule provides an array of modified derivatives. When applying (bio-)orthogonal reactions, protecting groups may not be necessary. Moreover, late-stage reactions show promise for bioorthogonal modification of biological macromolecules (e.g., proteins) even in complex biological matrices. As there are many functional groups present in biomolecules, side reactions might occur or some functional groups may be incompatible with the reaction conditions or might inhibit the reaction.

The thematic issue will focus on innovative orthogonal synthetic methods for peptide derivatization, e.g., by catalytic methods (transition metal catalysis, biocatalysis). More “classical” approaches, e.g., for conjugation purposes (CuAAC, RuAAC, IEDDA, etc.) will be considered only if the contributors document an innovative perspective.