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Green synthesis of bioactive oligopeptides promoted by recyclable nanocrystalline hydroxyapatite

    Michele Anselmi

    Department of Chemistry “Giacomo Ciamician”, University of Bologna, via Selmi 2, 40126 Bologna, Italy

    Authors contributed equally

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    ,
    Pasquale Stavole

    Department of Chemistry “Giacomo Ciamician”, University of Bologna, via Selmi 2, 40126 Bologna, Italy

    Authors contributed equally

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    ,
    Elisa Boanini

    Department of Chemistry “Giacomo Ciamician”, University of Bologna, via Selmi 2, 40126 Bologna, Italy

    ,
    Adriana Bigi

    Department of Chemistry “Giacomo Ciamician”, University of Bologna, via Selmi 2, 40126 Bologna, Italy

    ,
    Eusebio Juaristi

    Center for Research & Advanced Studies of the National Polytechnic Institute (Cinvestav), Av. Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Gustavo A. Madero, 07360 Mexico City, CDMX, Mexico

    &
    Luca Gentilucci

    *Author for correspondence: Tel.: +39 051 209 9570; Fax: +39 051 209 9456;

    E-mail Address: luca.gentilucci@unibo.it

    Department of Chemistry “Giacomo Ciamician”, University of Bologna, via Selmi 2, 40126 Bologna, Italy

    Published Online:https://doi.org/10.4155/fmc-2019-0320

    Aim: The pharmaceutical industry is showing renewed interest in therapeutic peptides. Unfortunately, the chemical synthesis of peptides remains very expensive and problematic in terms of environmental sustainability. Hence, making peptides ‘greener’ has become a new front line for the expansion of peptide market. Results: We developed a mechanochemical solvent-free peptide bond-forming protocol using standard reagents and nanocrystalline hydroxyapatite as a bio-compatible, reusable inorganic base. The reaction was also conducted under ultra-mild, minimal solvent-grinding conditions, using common laboratory equipment. Conclusion: The efficacy of the described protocol was validated with the convenient preparation of endomorphin-1, H-Tyr-Pro-Trp-Phe-NH2, the endogenous ligand of the μ-opioid receptor, currently regarded as a lead for the discovery of painkillers devoid of harmful side effects.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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