دورية أكاديمية
Rapid antibody conformational screening by matrix-assisted laser desorption/ionization hydrogen-deuterium exchange mass spectrometry.
| العنوان: | Rapid antibody conformational screening by matrix-assisted laser desorption/ionization hydrogen-deuterium exchange mass spectrometry. |
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| المؤلفون: | Mukherjee D; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Trigo-Mouriño P; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Jiang Y; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Nowak T; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Shchurik V; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Adpressa DA; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Louie MT; Absci Corp, Vancouver, Washington, USA., Reynolds SR; Absci Corp, Vancouver, Washington, USA., Hohn MJ; Merck & Co. Inc., Merck Research Laboratories, Bioprocess Research & Development, Boston, Massachusetts, USA., Al-Sayah MA; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Pirrone GF; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA., Makarov AA; Merck & Co. Inc., Merck Research Laboratories, Analytical Research & Development, Boston, Massachusetts, USA. |
| المصدر: | Journal of separation science [J Sep Sci] 2022 Jun; Vol. 45 (12), pp. 2055-2063. Date of Electronic Publication: 2022 Feb 16. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101088554 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1615-9314 (Electronic) Linking ISSN: 16159306 NLM ISO Abbreviation: J Sep Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Weinheim, Germany : Wiley-VCH, c2001- |
| مواضيع طبية MeSH: | Deuterium Exchange Measurement*/methods , Hydrogen*/chemistry, Deuterium/chemistry ; Deuterium/metabolism ; Lasers ; Proteins/chemistry ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization |
| مستخلص: | Recent advances in the field of cancer biology have accelerated the discovery and development of novel biopharmaceuticals. At the forefront of these drug development efforts are high-throughput screening, compressed timelines, and limited sample quantities, all characteristic of the discovery space. To meet program targets, large numbers of protein variants must be produced, screened, and characterized, presenting a daunting analytical challenge. Additionally, the higher-order structure is paramount for protein function and must be monitored as a critical quality attribute. Matrix-assisted laser desorption/ionization mass spectrometry has been utilized as an ultra-fast, automatable, sample-sparing analytical tool for biomolecules. Our group has published applications integrating hydrogen-deuterium exchange mass spectrometry with matrix-assisted laser desorption/ionization mass spectrometry for the rapid conformational characterization of small proteins, the current work expands this application to monoclonal and bi-specific antibodies. This study demonstrates the ability of the methodology, matrix-assisted laser desorption/ionization hydrogen-deuterium exchange mass spectrometry, to detect conformational differences between bi-specific antibodies from different expression hosts. These conformational differences were validated by orthogonal techniques including circular dichroism, nuclear magnetic resonance, and size-exclusion chromatography hydrogen-deuterium exchange mass spectrometry. This work demonstrates the utility of applying the developed methodology as a rapid conformational screening tool to triage samples for further analytical characterization. (© 2022 Wiley-VCH GmbH.) |
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| فهرسة مساهمة: | Keywords: cell-line development; hydrogen-deuterium exchange; monoclonal antibodies; protein conformation; ultra-high-throughput screening |
| المشرفين على المادة: | 0 (Proteins) 7YNJ3PO35Z (Hydrogen) AR09D82C7G (Deuterium) |
| تواريخ الأحداث: | Date Created: 20220202 Date Completed: 20220629 Latest Revision: 20220629 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1002/jssc.202100986 |
| PMID: | 35108448 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1615-9314 |
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| DOI: | 10.1002/jssc.202100986 |