Collagen targeting using multivalent protein-functionalized dendrimers
| Autor: | M Monica Breurken, Maarten Merkx, Brett A. Helms, Rinske P. Temming, E. W. Meijer, Edith H. M. Lempens |
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| Přispěvatelé: | Protein Engineering, Macromolecular and Organic Chemistry, Macro-Organic Chemistry |
| Rok vydání: | 2010 |
| Předmět: |
Dendrimers
Common disease Clinical Biochemistry Pharmaceutical Science Gene Expression Ligands Biochemistry Divalent Dendrimer Drug Discovery Animals Humans Cysteine Molecular Biology Targeting ligands chemistry.chemical_classification Binding protein Organic Chemistry Proteins Surface Plasmon Resonance Native chemical ligation Molecular Imaging Rats Tissue remodeling chemistry Biophysics Multivalency Molecular Medicine Collagen Plasmids Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry, 19(3), 1062-1071. Elsevier |
| ISSN: | 1464-3391 0968-0896 |
| Popis: | Collagen is an attractive marker for tissue remodeling in a variety of common disease processes. Here we report the preparation of protein dendrimers as multivalent collagen targeting ligands by native chemical ligation of the collagen binding protein CNA35 to cysteine-functionalized dendritic divalent (AB(2)) and tetravalent (AB(4)) wedges. The binding of these multivalent protein constructs was studied on collagen-immobilized chip surfaces as well as to native collagen in rat intestinal tissues. To understand the importance of target density we also created collagen-mimicking surfaces by immobilizing synthetic collagen triple helical peptides at various densities on a chip surface. Multivalent display of a weak-binding variant (CNA35-Y175K) resulted in a large increase in collagen affinity, effectively restoring the collagen imaging capacities for the AB(4) system. In addition, dissociation of these multivalent CNA35 dendrimers from collagen surfaces was found to be strongly attenuated. |
| Databáze: | OpenAIRE |
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