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NMR quality control of fragment libraries for screening
Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683495/ https://www.ncbi.nlm.nih.gov/pubmed/32533387 http://dx.doi.org/10.1007/s10858-020-00327-9 |
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author | Sreeramulu, Sridhar Richter, Christian Kuehn, Till Azzaoui, Kamal Blommers, Marcel Jules José Del Conte, Rebecca Fragai, Marco Trieloff, Nils Schmieder, Peter Nazaré, Marc Specker, Edgar Ivanov, Vladimir Oschkinat, Hartmut Banci, Lucia Schwalbe, Harald |
author_facet | Sreeramulu, Sridhar Richter, Christian Kuehn, Till Azzaoui, Kamal Blommers, Marcel Jules José Del Conte, Rebecca Fragai, Marco Trieloff, Nils Schmieder, Peter Nazaré, Marc Specker, Edgar Ivanov, Vladimir Oschkinat, Hartmut Banci, Lucia Schwalbe, Harald |
author_sort | Sreeramulu, Sridhar |
collection | PubMed |
description | Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of “poised fragments” with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10858-020-00327-9) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7683495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-76834952020-11-30 NMR quality control of fragment libraries for screening Sreeramulu, Sridhar Richter, Christian Kuehn, Till Azzaoui, Kamal Blommers, Marcel Jules José Del Conte, Rebecca Fragai, Marco Trieloff, Nils Schmieder, Peter Nazaré, Marc Specker, Edgar Ivanov, Vladimir Oschkinat, Hartmut Banci, Lucia Schwalbe, Harald J Biomol NMR Article Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of “poised fragments” with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10858-020-00327-9) contains supplementary material, which is available to authorized users. Springer Netherlands 2020-06-12 2020 /pmc/articles/PMC7683495/ /pubmed/32533387 http://dx.doi.org/10.1007/s10858-020-00327-9 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Sreeramulu, Sridhar Richter, Christian Kuehn, Till Azzaoui, Kamal Blommers, Marcel Jules José Del Conte, Rebecca Fragai, Marco Trieloff, Nils Schmieder, Peter Nazaré, Marc Specker, Edgar Ivanov, Vladimir Oschkinat, Hartmut Banci, Lucia Schwalbe, Harald NMR quality control of fragment libraries for screening |
title | NMR quality control of fragment libraries for screening |
title_full | NMR quality control of fragment libraries for screening |
title_fullStr | NMR quality control of fragment libraries for screening |
title_full_unstemmed | NMR quality control of fragment libraries for screening |
title_short | NMR quality control of fragment libraries for screening |
title_sort | nmr quality control of fragment libraries for screening |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683495/ https://www.ncbi.nlm.nih.gov/pubmed/32533387 http://dx.doi.org/10.1007/s10858-020-00327-9 |
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