Programmable bivalent peptide-DNA locks for pH-based control of antibody activity

Wouter Engelen, Kwankwan Zhu, Nikita Subedi, Andrea Idili, Francesco Ricci, Jurjen Tel, Maarten Merkx (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

8 Citaten (Scopus)
43 Downloads (Pure)

Samenvatting

The 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.

Originele taal-2Engels
Pagina's (van-tot)22-31
Aantal pagina's10
TijdschriftACS Central Science
Volume6
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 22 jan 2020

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