Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes

Abstract

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.

Dynamic covalent polymers for biomedical applications

“…The presence of redox agent or light source can also introduce corresponding structural and functional changes, which are compatible with some in vitro and in vivo tests. 34,35 Other than imines, nucleophilic addition/substitution reactions are often sufficiently reversible, especially when performed under the catalysis of acids or bases. Examples include trans(thiol)esterification, hemiacetal/hemiaminal reactions, nitroaldol addition, and conjugate addition reactions, where the biological sensitive functional groups, such as thiols, amines are embedded.…”

Dual stimuli-responsive dynamic covalent peptide tags: Towards sequence-controlled release in tumor-like microenvironments

“…The polar amino acid serine (S) was selected as a short spacer that provides sufficient water-solubility with no charges to prevent potential electrostatic repulsion in the spacers in contrast to our previous studies using lysine as a spacer. 26 S1-S4).…”

“…For solid-phase peptide synthesis (SPPS), the commercially available 4-boronophenylalanine (B) was protected in two steps with Fmoc and pinanediol on the amino and the BA functionality, respectively. 26 To study the event of multiple boronic acid-catechol interactions, sequences with one or two B and O residues, as well as one cysteine (C) per peptide were prepared, as shown in Scheme 1a and 1b. The polar amino acid serine (S) was selected as a short spacer that provides sufficient water-solubility with no charges to prevent potential electrostatic repulsion in the spacers in contrast to our previous studies using lysine as a spacer.…”

Solid‐Phase Protein Modifications: Towards Precision Protein Hybrids for Biological Applications

“…To this end, numerous designs have been developed over the last two decades using molecular bioconjugation reagents targeting natural and nonstandard amino acids, in vitro and in vivo , to address protein modifications in a precise manner, [16–22] as well as molecular reagents to induce defined protein assemblies that have been described in several excellent reviews [8,9,23,24] . Native chemical ligation has also been described to prepare synthetic proteins from amino acid building blocks with possibility to vary the stereochemistry and encoding of noncoded amino acids [25,26] .…”