Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes

[Image: see text] The development of a synthetic code that enables a sequence programmable feature like DNA represents a key aspect toward intelligent molecular systems. We developed herein the well-known dynamic covalent interaction between boronic acids (BAs) and catechols (CAs) into synthetic nucleobase analogs. Along a defined peptide backbone, BA or CA residues are arranged to enable sequence recognition to their complementary strand. Dynamic strand displacement and errors were elucidated thermodynamically to show that sequences are able to specifically select their partners. Unlike DNA, the pH dependency of BA/CA binding enables the dehybridization of complementary strands at pH 5.0. In addition, we demonstrate the sequence recognition at the macromolecular level by conjugating the cytochrome c protein to a complementary polyethylene glycol chain in a site-directed fashion.