Modular, bioorthogonal strategy for the controlled loading of cargo into a protein nanocage
| Autor: | Margo van der Pijl, Kimberly M. Bonger, Roeland J. M. Nolte, Mark B. van Eldijk, Selma Eising, Jaleesa Bresseleers, Lise Schoonen, Jan C. M. van Hest |
|---|---|
| Přispěvatelé: | Bio-Organic Chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Proton Magnetic Resonance Spectroscopy viruses Protein domain Biomedical Engineering Pharmaceutical Science Bioengineering 02 engineering and technology 010402 general chemistry 01 natural sciences Bio-Organic Chemistry Article chemistry.chemical_compound Capsid Carbon-13 Magnetic Resonance Spectroscopy GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Pharmacology Cowpea chlorotic mottle virus biology Organic Chemistry Proteins Bio-Molecular Chemistry 021001 nanoscience & nanotechnology biology.organism_classification Bromovirus 0104 chemical sciences Nanostructures chemistry Covalent bond Cyclization Drug delivery Biophysics Capsid Proteins Electrophoresis Polyacrylamide Gel Azide Bioorthogonal chemistry Nanocarriers 0210 nano-technology Physical Organic Chemistry Biotechnology |
| Zdroj: | Bioconjugate Chemistry Bioconjugate Chemistry, 29, 4, pp. 1186-1193 Bioconjugate Chemistry, 29(4), 1186-1193. American Chemical Society Bioconjugate Chemistry, 29, 1186-1193 |
| ISSN: | 1043-1802 1186-1193 |
| Popis: | Virus capsids, i.e., viruses devoid of their genetic material, are suitable nanocarriers for biomedical applications such as drug delivery and diagnostic imaging. For this purpose, the reliable encapsulation of cargo in such a protein nanocage is crucial, which can be accomplished by the covalent attachment of the compounds of interest to the protein domains positioned at the interior of the cage. This approach is particularly valid for the capsid proteins of the cowpea chlorotic mottle virus (CCMV), which have their N-termini located at the inside of the capsid structure. Here, we examined several site-selective modification methods for covalent attachment and encapsulation of cargo at the N-terminus of the CCMV protein. Initially, we explored approaches to introduce an N-terminal azide functionality, which would allow the subsequent bioorthogonal modification with a strained alkyne to attach the desired cargo. As these methods showed compatibility issues with the CCMV capsid proteins, a strategy based on 2-pyridinecarboxaldehydes for site-specific N-terminal protein modification was employed. This method allowed the successful modification of the proteins, and was applied for the introduction of a bioorthogonal vinylboronic acid moiety. In a subsequent reaction, the proteins could be modified further with a fluorophore using the tetrazine ligation. The application of capsid assembly conditions on the functionalized proteins led to successful particle formation, showing the potential of this covalent encapsulation strategy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|