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Influence of label and charge density on the association of the therapeutic monoclonal antibodies trastuzumab and cetuximab conjugated to anionic fluorophores

  • The design of bright and functional dye–protein conjugates requires hydrophilic and stable fluorophores with high molar absorption coefficients and high fluorescence quantum yields,which must not be prone to dimerization, as well as conservation of protein function and suppression of protein association. Although many synthetic dyes meet these needs, the influence of dye charge on bioconjugate performance is commonly neglected. This encouraged us to assess the spectroscopic properties, antibody functionality, binding behavior, folding, and association of conjugates of the therapeutic antibodies trastuzumab and cetuximab with the red cyanine dyes S0586, S2381,and 6SIDCC (bearing two, three, and six sulfonate Groups respectively. Our results demonstrate a negligible effect of dye labeling on antibody folding, yet a strong influence of Label charge and density on antibody isoelectric points and association.Especially 6SIDCC decreased strongly the isoelectric points of both antibodies andThe design of bright and functional dye–protein conjugates requires hydrophilic and stable fluorophores with high molar absorption coefficients and high fluorescence quantum yields,which must not be prone to dimerization, as well as conservation of protein function and suppression of protein association. Although many synthetic dyes meet these needs, the influence of dye charge on bioconjugate performance is commonly neglected. This encouraged us to assess the spectroscopic properties, antibody functionality, binding behavior, folding, and association of conjugates of the therapeutic antibodies trastuzumab and cetuximab with the red cyanine dyes S0586, S2381,and 6SIDCC (bearing two, three, and six sulfonate Groups respectively. Our results demonstrate a negligible effect of dye labeling on antibody folding, yet a strong influence of Label charge and density on antibody isoelectric points and association.Especially 6SIDCC decreased strongly the isoelectric points of both antibodies and their heavy or light chains even at low labeling degrees, thus favoring protein association. Although an increasingly negative dye charge reduces Antigen affinity as shown in a competitive immunoassay, all conjugates still bound to cells overexpressing the target of the respective antibody. Obviously, dyes that cause minimum dimerization with a small number of charged groups are best for conjugate brightness, minimum protein association, and strong target binding. This underlines the need to consider dye Charge for the rational design of conjugates with Optimum performance.zeige mehrzeige weniger

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Autor*innen:Jutta Pauli, Marieke Pochstein, A. Haase, J. Napp, A. Luch, Ute Resch-GengerORCiD
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):ChemBioChem
Jahr der Erstveröffentlichung:2016
Verlag:WILEY-VCH Verlag GmbH & Co. KGaA
Verlagsort:Weinheim
Jahrgang/Band:18
Ausgabe/Heft:1
Erste Seite:101
Letzte Seite:110
DDC-Klassifikation:Naturwissenschaften und Mathematik / Chemie / Analytische Chemie
Freie Schlagwörter:2D gel electrophoresis; Antibody; Fluorophore; Isoelectric point; Protein association
DOI:10.1002/cbic.201600299
ISSN:1439-7633
ISSN:1439-4227
Verfügbarkeit des Dokuments:Datei im Netzwerk der BAM verfügbar ("Closed Access")
Datum der Freischaltung:10.01.2017
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:10.03.2017
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