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Biocompatible Size‐Defined Dendrimer–Albumin Binding Protein Hybrid Materials as a Versatile Platform for Biomedical Applications
Authors:Jan Maly  Ondrej Stanek  Jan Frolik  Marek Maly  Franka Ennen  Dietmar Appelhans  Alena Semeradtova  Dominika Wrobel  Marcel Stofik  Tereza Knapova  Milan Kuchar  Lucie Cervenkova Stastna  Jan Cermak  Peter Sebo  Petr Maly
Affiliation:1. Department of Biology, Faculty of Science, ústí nad Labem, Czech Republic;2. Institute of Biotechnology CAS, v. v. i, Jesenice u Prahy, Czech Republic;3. Leibniz Institute of Polymer Research Dresden, Dresden, Germany;4. Institute of Chemical Process Fundamentals CAS, v. v. i, Prague, Czech Republic;5. Institute of Microbiology CAS, v. v. i, Prague, Czech Republic
Abstract:
For the design of a biohybrid structure as a ligand‐tailored drug delivery system (DDS), it is highly sophisticated to fabricate a DDS based on smoothly controllable conjugation steps. This article reports on the synthesis and the characterization of biohybrid conjugates based on noncovalent conjugation between a multivalent biotinylated and PEGylated poly(amido amine) (PAMAM) dendrimer and a tetrameric streptavidin‐small protein binding scaffold. This protein binding scaffold (SA‐ABDwt) possesses nM affinity toward human serum albumin (HSA). Thus, well‐defined biohybrid structures, finalized by binding of one or two HSA molecules, are available at each conjugation step in a controlled molar ratio. Overall, these biohybrid assemblies can be used for (i) a controlled modification of dendrimers with the HSA molecules to increase their blood‐circulation half‐life and passive accumulation in tumor; (ii) rendering dendrimers a specific affinity to various ligands based on mutated ABD domain, thus replacing tedious dendrimer–antibody covalent coupling and purification procedures.
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Keywords:binding domain proteins  biohybrid structures  HSA  PAMAM dendrimer  Streptavidin‐biotin conjugations
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