Identification of Molecular-Mimicry-Based Ligands for Cholera Diagnostics using Magnetic Relaxation

    Authors

    C. Kaittanis; T. Banerjee; S. Santra; O. J. Santiesteban; K. Teter;J. M. Perez

    Comments

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    Abbreviated Journal Title

    Bioconjugate Chem.

    Keywords

    STAPHYLOCOCCAL-ENTEROTOXIN-B; HEAT-LABILE ENTEROTOXIN; BACILLUS-ANTHRACIS; ESCHERICHIA-COLI; MASS-SPECTROMETRY; TOXIN; NANOPARTICLE; BIOSENSOR; CELLS; GANGLIOSIDES; Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic

    Abstract

    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.

    Journal Title

    Bioconjugate Chemistry

    Volume

    22

    Issue/Number

    2

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    307

    Last Page

    314

    WOS Identifier

    WOS:000287297000025

    ISSN

    1043-1802

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