oc9b00964_si_001.pdf (2.1 MB)
Programmable Bivalent Peptide–DNA Locks for pH-Based Control of Antibody Activity
journal contribution
posted on 2019-12-23, 12:34 authored by Wouter Engelen, Kwankwan Zhu, Nikita Subedi, Andrea Idili, Francesco Ricci, Jurjen Tel, Maarten MerkxThe ability to control antibody activity by pH has important
applications
in diagnostics, therapeutic antibody targeting, and antibody-guided
imaging. Here, we report the rational design of bivalent peptide–DNA
ligands that allow pH-dependent control of antibody activity. Our
strategy uses a pH-responsive DNA triple helix to control switching
from a tight-binding bivalent peptide–DNA lock into a weaker-binding
monovalent ligand. Different designs are introduced that allow antibody
activation at both basic and acidic pHs, either autonomously or in
the presence of an additional oligonucleotide trigger. The pH of antibody
activation could be precisely tuned by changing the DNA triple helix
sequence. The peptide–DNA locks allowed pH-dependent antibody
targeting of tumor cells both in bulk and for single cells confined
in water-in-oil microdroplets. The latter approach enables high-throughput
antibody-mediated detection of single tumor cells based on their distinctive
metabolic activity.