Conjugation, immunoreactivity, and immunogenicity of calix[4]arenes; model study to potential calix[4]arene-based Ac3+ chelators

Grote Gansey, Marcel H.B. and Haan de, Annemarie S. and Bos, Ebo S. and Verboom, Willem and Reinhoudt, David N. (1999) Conjugation, immunoreactivity, and immunogenicity of calix[4]arenes; model study to potential calix[4]arene-based Ac3+ chelators. Bioconjugate Chemistry, 10 (4). pp. 613-623. ISSN 1043-1802

PDF
Restricted to UT campus only: Request a copy
150Kb

Abstract:	For the development of calix[4]arene-based radiotherapeutic agents, the conjugation to biomolecules and immunogenicity in mice of potential 225Ac3+-chelating calix[4]arenes were studied. A calix[4]arene triethyl ester isothiocyanate and a bis(calix[4]arene) hexacarboxylic acid, containing a masked thiol functionality, were used in conjugation experiments to a mouse monoclonal antibody and serum albumins. All characterization techniques indicate that only the calix[4]arene carboxylic acid is successfully conjugated to the biomolecules. The immunoreactivity of the conjugates is not impaired when up to 6 equiv of calixarene are bound to the monoclonal antibody. Animal tests indicated that the immunogenicity toward the calix[4]arene is strongly influenced by the nature of the carrier, the dosage, and the injection method. No immune response occurred when a homologous carrier was used or when a heterologous carrier was applied at a dosage of 10 μg per immunization via intravenous injection. Under all other conditions, the presence of antibodies directed against the calix[4]arene was demonstrated. Thus, for the application in radioimmunotherapy, the conjugation of a calix[4]arene to a humanized antibody will probably not lead to an immune response, and the immunoreactivity will not be disturbed.
Item Type:	Article
Copyright:	© 2009 American Chemical Society
Faculty:	Science and Technology (TNW)
Research Group:	Molecular Nanofabrication (MNF)
Link to this item:	http://purl.utwente.nl/publications/11019
Official URL:	http://dx.doi.org/10.1021/bc9801474
Export this item as:	BibTeX EndNote HTML Citation Reference Manager

Show download statistics for this publication

Repository Staff Only: item control page

Metis ID: 105953