Cross-conjugation of DNA, proteins and peptidesvia a pH switch

Abstract

The design of an orthogonal, thiol-reactive cross-conjugation reagent is presented that allows step-wise and site-selective combination of biomacromolecules such as proteins, peptides or oligonucleotides by simply adjusting the pH. Both reaction centers of this versatile bioconjugation reagent are located at opposite sites leaving sufficient space for combining even sterically demanding molecules. Our results are of high significance and general applicability for the preparation of defined peptide–protein, protein–protein or protein–DNA conjugates and pave the way to tailored biotherapeutics.