Identification of Molecular-Mimicry-Based Ligands for Cholera Diagnostics using Magnetic Relaxation
| Autor: | Oscar J. Santiesteban, Tuhina Banerjee, J. Manuel Perez, Charalambos Kaittanis, Ken Teter, Santimukul Santra |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cholera Toxin
Stereochemistry Molecular Conformation Biomedical Engineering Pharmaceutical Science Nanoparticle Bioengineering G(M1) Ganglioside Conjugated system Ligands medicine.disease_cause Ferric Compounds complex mixtures Article Magnetics chemistry.chemical_compound Cholera Chlorocebus aethiops medicine Animals Surface plasmon resonance Vero Cells Pharmacology Ligand Cell Membrane Molecular Mimicry Organic Chemistry Relaxation (NMR) Galactose Dextrans Surface Plasmon Resonance Molecular mimicry chemistry Covalent bond embryonic structures Biophysics Nanoparticles Iron oxide nanoparticles Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 22:307-314 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc100442q |
| Popis: | When covalently bound to an appropriate ligand, iron oxide nanoparticles can bind to a specific target of interest. This interaction can be detected through changes in the solution's spin-spin relaxation times (T2) via magnetic relaxation measurements. In this report, a strategy of molecular mimicry was used in order to identify targeting ligands that bind to the cholera toxin B subunit (CTB). The cellular CTB-receptor, ganglioside GM1, contains a pentasaccharide moiety consisting in part of galactose and glucose units. We therefore predicted that CTB would recognize carbohydrate-conjugated iron oxide nanoparticles as GM1 mimics, thus producing a detectable change in the T2 relaxation times. Magnetic relaxation experiments demonstrated that CTB interacted with the galactose-conjugated nanoparticles. This interaction was confirmed via surface plasmon resonance studies using either the free or nanoparticle-conjugated galactose molecule. The galactose-conjugated nanoparticles were then used as CTB sensors achieving a detection limit of 40 pM. Via magnetic relaxation studies, we found that CTB also interacted with dextran-coated nanoparticles, and surface plasmon resonance studies also confirmed this interaction. Additional experiments demonstrated that the dextran-coated nanoparticle can also be used as CTB sensors and that dextran can prevent the internalization of CTB into GM1-expressing cells. Our work indicates that magnetic nanoparticle conjugates and magnetic relaxation detection can be used as a simple and fast method to identify targeting ligands via molecular mimicry. Furthermore, our results show that the dextran-coated nanoparticles represent a low-cost approach for CTB detection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|