Dissociation mechanics and stability of type A botulinum neurotoxin complex by means of biophysical evaluation
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Hada, S. | - |
dc.contributor.author | Lee, J.C. | - |
dc.contributor.author | Lee, E.C. | - |
dc.contributor.author | Ji, S. | - |
dc.contributor.author | Nam, J.S. | - |
dc.contributor.author | Yun, B.J. | - |
dc.contributor.author | Na, D.H. | - |
dc.contributor.author | Kim, N.A. | - |
dc.contributor.author | Jeong, S.H. | - |
dc.date.accessioned | 2022-05-04T02:40:16Z | - |
dc.date.available | 2022-05-04T02:40:16Z | - |
dc.date.issued | 2022-07 | - |
dc.identifier.issn | 2093-5552 | - |
dc.identifier.issn | 2093-6214 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/57123 | - |
dc.description.abstract | Purpose: Biophysical characterisation of type A botulinum neurotoxin (BoNT/A) could be challenging since it exists in association with neurotoxin associated proteins (NAPs) as large protein complexes. The objective of this study was to elucidate the dissociation mechanics of BoNT/A complex along with its thermodynamic stability through a combination of analytical tools. Methods: Size exclusion chromatography (SEC) was mainly used to study the behavior of BoNT/A complex at various pH. In addition, multi-angled light scattering (MALS), enzyme linked immunosorbent assay (ELISA), and dynamic light scattering (DLS) were utilized to validate its chromatographic results. Results: The dissociation of BoNT/A from its complex was found to be strongly dependent on its pH with higher dissociation towards alkaline pH which was further accelerated with time and temperature. In addition, dissociated BoNT/A at pH 7.4 showed lower thermal stability compared to the associated state even in the presence of polysorbate, as revealed by the SEC chromatogram and aggregation onset temperature. Moreover, the partial reversibility of the dissociated BoNT/A complex after titration of pH to 6.0, suggested vulnerability of BoNT/A towards formation of irreversible aggregates as it dissociates, signifying lower stability profile of the neurotoxin after dissociation. Conclusion: Overall, BoNT/A was more stable when associated with NAPs at pH 6.0 compared to its dissociated state at pH 7.4. Moreover, the conventional analytical used could be utilized to relatively quantify its amount in different formulations. © 2022, The Author(s) under exclusive licence to The Korean Society of Pharmaceutical Sciences and Technology. | - |
dc.format.extent | 11 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Springer | - |
dc.title | Dissociation mechanics and stability of type A botulinum neurotoxin complex by means of biophysical evaluation | - |
dc.title.alternative | Dissociation mechanics and stability of type A botulinum neurotoxin complex by means of biophysical evaluation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1007/s40005-022-00570-2 | - |
dc.identifier.bibliographicCitation | Journal of Pharmaceutical Investigation, v.52, no.4, pp 453 - 463 | - |
dc.identifier.kciid | ART002861714 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000782165500001 | - |
dc.identifier.scopusid | 2-s2.0-85127676063 | - |
dc.citation.endPage | 463 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 453 | - |
dc.citation.title | Journal of Pharmaceutical Investigation | - |
dc.citation.volume | 52 | - |
dc.type.docType | Article | - |
dc.publisher.location | 대한민국 | - |
dc.subject.keywordAuthor | Biophysical characterization | - |
dc.subject.keywordAuthor | Botulinum neurotoxin A complex | - |
dc.subject.keywordAuthor | Formulation | - |
dc.subject.keywordAuthor | Neurotoxin stability | - |
dc.subject.keywordAuthor | Protein aggregation | - |
dc.subject.keywordAuthor | Size-exclusion chromatography (SEC) | - |
dc.subject.keywordPlus | TOXIN TYPE-A | - |
dc.subject.keywordPlus | ENDOPEPTIDASE ACTIVITY | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | PH | - |
dc.subject.keywordPlus | PROTECTION | - |
dc.subject.keywordPlus | COMPONENT | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
84, Heukseok-ro, Dongjak-gu, Seoul, Republic of Korea (06974)02-820-6194
COPYRIGHT 2019 Chung-Ang University All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.