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Polymers 2018, 10(2), 141; https://doi.org/10.3390/polym10020141

Site-Specific DBCO Modification of DEC205 Antibody for Polymer Conjugation

1
Institute of Organic Chemistry, Johannes-Gutenberg University Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany
2
Graduate School Materials Science in Mainz, Staudingerweg 9, D-55128 Mainz, Germany
3
Max-Planck-Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany
4
Institute of Physical Chemistry, Jakob Welder Weg 11, D-55128 Mainz, Germany
*
Author to whom correspondence should be addressed.
Received: 14 January 2018 / Revised: 29 January 2018 / Accepted: 30 January 2018 / Published: 2 February 2018
(This article belongs to the Special Issue Polymers for Therapy and Diagnostics)
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Abstract

The design of multifunctional polymer-based vectors, forming pDNA vaccines, offers great potential in cancer immune therapy. The transfection of dendritic immune cells (DCs) with tumour antigen-encoding pDNA leads to an activation of the immune system to combat tumour cells. In this work, we investigated the chemical attachment of DEC205 antibodies (aDEC205) as DC-targeting structures to polyplexes of P(Lys)-b-P(HPMA). The conjugation of a synthetic block copolymer and a biomacromolecule with various functionalities (aDEC205) requires bioorthogonal techniques to avoid side reactions. Click chemistry and in particular the strain-promoted alkyne-azide cycloaddition (SPAAC) can provide the required bioorthogonality. With regard to a SPAAC of both components, we firstly synthesized two different azide-containing block copolymers, P(Lys)-b-P(HPMA)-N3(stat) and P(Lys)-b-P(HPMA)-N3(end), for pDNA complexation. In addition, the site-specific incorporation of ring-strained dibenzocyclooctyne (DBCO) moieties to the DEC205 antibody was achieved by an enzymatic strategy using bacterial transglutaminase (BTG). The chemical accessibility of DBCO molecules within aDEC205 as well as the accessibility of azide-functionalities on the polyplex’ surface were investigated by various SPAAC experiments and characterized by fluorescence correlation spectroscopy (FCS). View Full-Text
Keywords: cancer immune therapy; vaccination; dendritic cells (DCs); pDNA polyplex; RAFT polymerization; targeting; DEC205 antibody; bioorthogonal chemistry; strain-promoted alkyne-azide cycloaddition (SPAAC) cancer immune therapy; vaccination; dendritic cells (DCs); pDNA polyplex; RAFT polymerization; targeting; DEC205 antibody; bioorthogonal chemistry; strain-promoted alkyne-azide cycloaddition (SPAAC)
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Beck, S.; Schultze, J.; Räder, H.-J.; Holm, R.; Schinnerer, M.; Barz, M.; Koynov, K.; Zentel, R. Site-Specific DBCO Modification of DEC205 Antibody for Polymer Conjugation. Polymers 2018, 10, 141.

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