Multivalent Cluster Nanomolecules for Inhibiting Protein–Protein Interactions
| Autor: | Yanxiao Han, Elaine A. Qian, Marco S. Messina, Alexander M. Spokoyny, Petr Král, Heather D. Maynard |
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| Rok vydání: | 2019 |
| Předmět: |
Cell signaling
Protein Conformation Biomedical Engineering Pharmaceutical Science Receptors Cell Surface Bioengineering 02 engineering and technology Computational biology HIV Envelope Protein gp120 Molecular Dynamics Simulation 01 natural sciences Article Protein–protein interaction Engineering Cell Adhesion Cluster (physics) Lectins C-Type Pharmacology 010405 organic chemistry Chemistry Organic Chemistry Adhesion 021001 nanoscience & nanotechnology Nanostructures 0104 chemical sciences 0210 nano-technology Cell Adhesion Molecules Protein Binding Signal Transduction Biotechnology |
| Zdroj: | Bioconjug Chem |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.9b00526 |
| Popis: | Multivalent protein-protein interactions serve central roles in many essential biological processes, ranging from cell signaling and adhesion to pathogen recognition. Uncovering the rules that govern these intricate interactions is important not only to basic biology and chemistry, but also to the applied sciences where researchers are interested in developing molecules to promote or inhibit these interactions. Here we report the synthesis and application of atomically precise inorganic cluster nanomolecules consisting of an inorganic core and a covalently linked densely-packed layer of saccharides. These hybrid agents are stable under biologically relevant conditions and exhibit multivalent binding capabilities, which enable us to study the complex interactions between glycosylated structures and a dendritic cell lectin receptor. Importantly, we find that subtle changes in the molecular structure lead to significant differences in the nanomolecule’s protein-binding properties. Furthermore, we demonstrate an example of using these hybrid nanomolecules to effectively inhibit protein-protein interactions in a human cell line. Ultimately, this work reveals an intricate interplay between the structural design of multivalent agents and their biological activities toward protein surfaces. |
| Databáze: | OpenAIRE |
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