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Thermodynamic and kinetic approaches for evaluation of monoclonal antibody - Lipoprotein interactions.
University of Helsinki, Finland..ORCID iD: 0000-0002-8717-8842
Uppsala universitet.
Uppsala universitet.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences (from 2013).ORCID iD: 0000-0003-1819-1709
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2016 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 518, p. 25-34Article in journal (Refereed) Published
Abstract [en]

Two complementary instrumental techniques were used, and the data generated was processed with advanced numerical tools to investigate the interactions between anti-human apoB-100 monoclonal antibody (anti-apoB-100 Mab) and apoB-100 containing lipoproteins. Partial Filling Affinity Capillary Electrophoresis (PF-ACE) combined with Adsorption Energy Distribution (AED) calculations provided information on the heterogeneity of the interactions without any a priori model assumptions. The AED calculations evidenced a homogenous binding site distribution for the interactions. Quartz Crystal Microbalance (QCM) studies were used to evaluate thermodynamics and kinetics of the Low-Density Lipoprotein (LDL) and anti-apoB-100 Mab interactions. High affinity and selectivity were observed, and the emerging data sets were analysed with so called Interaction Maps. In thermodynamic studies, the interaction between LDL and anti-apoB-100 Mab was found to be predominantly enthalpy driven. Both techniques were also used to study antibody interactions with Intermediate-Density (IDL) and Very Low-Density (VLDL) Lipoproteins. By screening affinity constants for IDL-VLDL sample in a single injection we were able to distinguish affinity constants for both subpopulations using the numerical Interaction Map tool.

Place, publisher, year, edition, pages
Academic Press, 2016. Vol. 518, p. 25-34
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Chemical Sciences
Research subject
Chemistry
Identifiers
URN: urn:nbn:se:kau:diva-47574DOI: 10.1016/j.ab.2016.10.024ISI: 000392461000004PubMedID: 27984014OAI: oai:DiVA.org:kau-47574DiVA, id: diva2:1061990
Available from: 2017-01-04 Created: 2017-01-04 Last updated: 2020-05-22Bibliographically approved

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Samuelsson, JörgenForssén, PatrikFornstedt, Torgny

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