Label-free drug interaction screening via Raman microscopy
Abstract
Development of a simple, label-free screening technique capable of precisely and directly sensing interaction-in-solution over a size range from small molecules to large proteins such as antibodies could offer an important tool for researchers and pharmaceutical companies in the field of drug development. In this work, we present a thermostable Raman interaction profiling (TRIP) technique that facilitates low-concentration and low-dose screening of binding between protein and ligand in physiologically relevant conditions. TRIP was applied to eight protein–ligand systems, and produced reproducible high-resolution Raman measurements, which were analyzed by principal component analysis. TRIP was able to resolve time-depending binding between 2,4-dinitrophenol and transthyretin, and analyze biologically relevant SARS-CoV-2 spike-antibody interactions. Mixtures of the spike receptor–binding domain with neutralizing, nonbinding, or binding but nonneutralizing antibodies revealed distinct and reproducible Raman signals. TRIP holds promise for the future developments of high-throughput drug screening and real-time binding measurements between protein and drug.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 18, 2023
- Source ID
- 10.1073/pnas.2218826120
Entities
People
- Alexei Sokolov
- Benjamin W. Neuman
- Marlan Scully
- Narangerel Altangerel
- Navid Rajil
- Philip Hemmer
- Vladislav V Yakovlev
- Zhenhuan Yi
Organizations
- Air Force Office of Scientific Research
- Baylor University
- Foundation for the National Institutes of Health
- Office of Naval Research
- Princeton University
- Robert A. Welch Foundation