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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 develo...

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Autores principales: Altangerel, Narangerel, Neuman, Benjamin W., Hemmer, Philip R., Yakovlev, Vladislav V., Rajil, Navid, Yi, Zhenhuan, Sokolov, Alexei V., Scully, Marlan O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372630/
https://www.ncbi.nlm.nih.gov/pubmed/37463207
http://dx.doi.org/10.1073/pnas.2218826120
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author Altangerel, Narangerel
Neuman, Benjamin W.
Hemmer, Philip R.
Yakovlev, Vladislav V.
Rajil, Navid
Yi, Zhenhuan
Sokolov, Alexei V.
Scully, Marlan O.
author_facet Altangerel, Narangerel
Neuman, Benjamin W.
Hemmer, Philip R.
Yakovlev, Vladislav V.
Rajil, Navid
Yi, Zhenhuan
Sokolov, Alexei V.
Scully, Marlan O.
author_sort Altangerel, Narangerel
collection PubMed
description 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.
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spelling pubmed-103726302023-07-28 Label-free drug interaction screening via Raman microscopy Altangerel, Narangerel Neuman, Benjamin W. Hemmer, Philip R. Yakovlev, Vladislav V. Rajil, Navid Yi, Zhenhuan Sokolov, Alexei V. Scully, Marlan O. Proc Natl Acad Sci U S A Physical Sciences 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. National Academy of Sciences 2023-07-18 2023-07-25 /pmc/articles/PMC10372630/ /pubmed/37463207 http://dx.doi.org/10.1073/pnas.2218826120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Physical Sciences
Altangerel, Narangerel
Neuman, Benjamin W.
Hemmer, Philip R.
Yakovlev, Vladislav V.
Rajil, Navid
Yi, Zhenhuan
Sokolov, Alexei V.
Scully, Marlan O.
Label-free drug interaction screening via Raman microscopy
title Label-free drug interaction screening via Raman microscopy
title_full Label-free drug interaction screening via Raman microscopy
title_fullStr Label-free drug interaction screening via Raman microscopy
title_full_unstemmed Label-free drug interaction screening via Raman microscopy
title_short Label-free drug interaction screening via Raman microscopy
title_sort label-free drug interaction screening via raman microscopy
topic Physical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372630/
https://www.ncbi.nlm.nih.gov/pubmed/37463207
http://dx.doi.org/10.1073/pnas.2218826120
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