Michele Anselmi1, Pasquale Stavole1, Elisa Boanini1, Adriana Bigi1, Eusebio Juaristi2, Luca Gentilucci1. 1. Department of Chemistry "Giacomo Ciamician", University of Bologna, via Selmi 2, 40126 Bologna, Italy. 2. 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.
Abstract
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.
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.