Monovinyl Sulfone β-Cyclodextrin. A Flexible Drug Carrier System

Authors

  • Dr. Teresa del Castillo,

    1. Hospital Universitario San Cecilio, Instituto de Investigaciones Biosanitarias de Granada, FIBAO, Granada (Spain)
    2. Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada (Spain)
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    • These authors contributed equally to this work.

  • Dr. Julia Marales-Sanfrutos,

    1. Departamento de Química Orgánica, Instituto de Biotecnología, Universidad de Granada, 18071 Granada (Spain)
    2. Current address: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, OX1 3TA Oxford (UK)
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    • These authors contributed equally to this work.

  • Prof. Francisco Santoyo-González,

    1. Departamento de Química Orgánica, Instituto de Biotecnología, Universidad de Granada, 18071 Granada (Spain)
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  • Dr. Stefan Magez,

    1. Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels (Belgium)
    2. Department of Molecular and Cellular Interactions, VIB, Brussels (Belgium)
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  • Dr. F. Javier Lopez-Jaramillo,

    Corresponding author
    1. Departamento de Química Orgánica, Instituto de Biotecnología, Universidad de Granada, 18071 Granada (Spain)
    • Departamento de Química Orgánica, Instituto de Biotecnología, Universidad de Granada, 18071 Granada (Spain)

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  • Dr. Jose A. Garcia-Salcedo

    1. Hospital Universitario San Cecilio, Instituto de Investigaciones Biosanitarias de Granada, FIBAO, Granada (Spain)
    2. Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada (Spain)
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Abstract

Cyclodextrins have been conjugated to target various receptors and have also been functionalized with carbohydrates for targeting specific organs. However, this approach is based on a rigid design that implies the ad hoc synthesis of each cyclodextrin-targeting agent conjugate. We hypothesized that: 1) a modular design that decouples the carrier function from the targeting function leads to a flexible system, 2) combining the reactivity of the vinyl sulfone group toward biomolecules that act as targeting agents with the ability of cyclodextrin to form complexes with a wide range of drugs may yield a versatile system that allows the targeting of different organs with different drugs, and 3) the higher reactivity of histidine residues toward the vinyl sulfone group can be exploited to couple the cyclodextrin to the targeting system with a degree of regioselectivity. As a proof of concept, we synthesized a monovinyl sulfone β-cyclodextrin (module responsible for the payload), which, after coupling to recombinant antibody fragments raised against Trypanosoma brucei (module responsible for targeting) and loading with nitrofurazone (module responsible for therapeutic action) resulted in an effective delivery system that targets the surface of the parasites and shows trypanocidal activity.

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