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Title: Label-free drug interaction screening via Raman microscopy
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.  more » « less
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Proceedings of the National Academy of Sciences
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Sponsoring Org:
National Science Foundation
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    Basic Protocol: SARS‐CoV‐2 antibody detection using the split‐luciferase assay on a medium‐throughput scale with a laboratory luminometer

    Alternate Protocol 1: High‐throughput‐based protocol for SARS‐CoV‐2 antibody detection using a robotic platform

    Alternate Protocol 2: Point‐of‐care‐based protocol for SARS‐CoV‐2 antibody detection using a handheld luminometer

    Support Protocol: Determining positive/negative cutoffs for test samples and standardizing the assay between days

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