دورية أكاديمية
Interrogation of solution conformation of complex macrocyclic peptides utilizing a combined SEC-HDX-MS, circular dichroism, and NMR workflow.
| العنوان: | Interrogation of solution conformation of complex macrocyclic peptides utilizing a combined SEC-HDX-MS, circular dichroism, and NMR workflow. |
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| المؤلفون: | Adpressa DA; Analytical Research & Development, Merck & Co. Inc., Boston, Massachusetts 02115, USA. alexey.makarov@merck.com., Reibarkh M; Analytical Research & Development, Merck & Co. Inc., Rahway, New Jersey 07065, USA. mikhail_reibarkh@merck.com., Jiang Y; Analytical Research & Development, Merck & Co. Inc., Boston, Massachusetts 02115, USA. alexey.makarov@merck.com., Saurí J; Analytical Research & Development, Merck & Co. Inc., Boston, Massachusetts 02115, USA. alexey.makarov@merck.com., Makarov AA; Analytical Research & Development, Merck & Co. Inc., Boston, Massachusetts 02115, USA. alexey.makarov@merck.com. |
| المصدر: | The Analyst [Analyst] 2022 Jan 17; Vol. 147 (2), pp. 325-332. Date of Electronic Publication: 2022 Jan 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 0372652 Publication Model: Electronic Cited Medium: Internet ISSN: 1364-5528 (Electronic) Linking ISSN: 00032654 NLM ISO Abbreviation: Analyst Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge : Royal Society of Chemistry Original Publication: London : Chemical Society |
| مواضيع طبية MeSH: | Deuterium Exchange Measurement* , Hydrogen Deuterium Exchange-Mass Spectrometry*, Circular Dichroism ; Peptides ; Protein Conformation ; Workflow |
| مستخلص: | Recent technological and synthetic advances have led to a resurgence in the exploration of peptides as potential therapeutics. Understanding peptide conformation in both free and protein-bound states remains one of the most critical areas for successful development of peptide drugs. In this study it was demonstrated that the combination of Size-Exclusion Chromatography with Hydrogen-Deuterium Exchange Mass Spectrometry (SEC-HDX-MS) and Circular Dichroism Spectroscopy (CD) can be used to guide the selection of peptides for further NMR analysis. Moreover, the insights from this workflow guide the choice of the best biologically relevant conditions for NMR conformational studies of peptide ligands in a free state in solution. Combined information about solution conformation character and stability across temperatures and co-solvent compositions greatly expedites selection of optimal conditions for NMR analysis. In total, the combination of SEC-HDX-MS, CD, and NMR into a single complementary workflow greatly accelerates conformational analysis of peptides in the drug discovery lead optimization process. |
| المشرفين على المادة: | 0 (Peptides) |
| تواريخ الأحداث: | Date Created: 20211220 Date Completed: 20220119 Latest Revision: 20220119 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1039/d1an01619a |
| PMID: | 34927633 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1364-5528 |
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| DOI: | 10.1039/d1an01619a |