Synthesis and Biophysical Study of Disassembling Nanohybrid Bioconjugates with a Cubic Octasilsesquioxane Core

Authors

  • Beatriz Trastoy,

    1. Instituto de Química Orgánica General (IQOG), CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
    Current affiliation:
    1. Institute of Human Virology, University of Maryland, School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
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  • Daniel A. Bonsor,

    1. Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Current affiliation:
    1. Institute of Human Virology, University of Maryland, School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
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  • M. Eugenia Pérez-Ojeda,

    1. Instituto de Química-Física “Rocasolano” (IQFR), CSIC, Serrano 119, 28006 Madrid, Spain
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  • M. Luisa Jimeno,

    1. Centro de Química Orgánica “Manuel Lora Tamayo” (CENQUIOR), CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
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  • Alejandro Méndez-Ardoy,

    1. Instituto de Investigaciones Químicas (IIQ), CSIC–Universidad de Sevilla, Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain
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  • José Manuel García Fernández,

    1. Instituto de Investigaciones Químicas (IIQ), CSIC–Universidad de Sevilla, Américo Vespucio 49, Isla de la Cartuja, 41092 Sevilla, Spain
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  • Eric J. Sundberg,

    Corresponding author
    1. Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
    Current affiliation:
    1. Institute of Human Virology, University of Maryland, School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USA
    • Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA
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  • Jose Luis Chiara

    Corresponding author
    1. Instituto de Química Orgánica General (IQOG), CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
    • Instituto de Química Orgánica General (IQOG), CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
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Abstract

Polyhedral oligosilsesquioxanes (POSS) have recently attracted attention as scaffolds for the synthesis of multivalent bioconjugates. The synthesis of glycosyl-octasilsesquioxanes (glyco-POSS) using a copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition approach is reported. The problems associated with the use of bases or aqueous media in their preparation are investigated and a comprehensive study of the multivalent interaction between the mannosyl-octasilsesquioxanes and a model lectin, concanavalin A (Con A), using an array of complementary biophysical techniques is presented. The possibility to modulate the half-life of POSS conjugates in aqueous solution and the low toxicity of their constituent monomeric organosilanes offers an advantage over other scaffolds in vivo, preventing bioaccumulation and saturation of complementary receptors (lectins). Despite the hydrolysis in water, the octamannosyl-POSS studied shows a 50-fold higher binding affinity to Con A than methyl α-D-mannopyranoside. These experiments suggest that the novel glyco-POSS are attractive compounds for in vivo applications that require multivalent display of glycans.

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