Programmable Bivalent Peptide-DNA Locks for pH-Based Control of Antibody Activity
Wouter Engelen1,2, Kwankwan Zhu1,2, Nikita Subedi2,3
1Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven 5600 MB, The Netherlands.
ACS Central Science
|January 29, 2020
Summary
Researchers developed pH-switchable peptide-DNA ligands to control antibody activity for diagnostics and therapeutics. This innovation enables precise, tunable antibody targeting and detection of single tumor cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Biotechnology
Background:
- Controlling antibody activity via pH is crucial for applications in diagnostics, targeted therapy, and imaging.
- Existing methods for pH-dependent antibody control are limited.
Purpose of the Study:
- To rationally design bivalent peptide-DNA ligands for pH-dependent control of antibody activity.
- To enable tunable antibody activation at specific pH ranges for various applications.
Main Methods:
- Utilized a pH-responsive DNA triple helix to switch between bivalent and monovalent antibody binding modes.
- Engineered different peptide-DNA ligand designs for autonomous or triggered antibody activation.
- Tuned the pH-sensitivity by altering the DNA triple helix sequence.
- Applied peptide-DNA locks for pH-dependent tumor cell targeting in bulk and single-cell microdroplet formats.
Main Results:
- Successfully designed peptide-DNA ligands that modulate antibody activity based on pH.
- Demonstrated precise tuning of antibody activation pH by modifying DNA sequences.
- Achieved pH-dependent antibody targeting of tumor cells in both bulk and single-cell assays.
- Enabled high-throughput detection of single tumor cells using pH-triggered antibody activity.
Conclusions:
- Peptide-DNA ligands offer a versatile platform for pH-controlled antibody function.
- This technology has significant potential for advancing diagnostics, therapeutics, and imaging.
- The single-cell microdroplet approach facilitates novel high-throughput cell detection methods.
