Tomasz M Goszczyński1, Konrad Kowalski2, Zbigniew J Leśnikowski3, Janusz Boratyński2. 1. "Neolek" Laboratory of Biomedical Chemistry, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, PAS, 12 Rudolf Weigl St., 53-114 Wrocław, Poland. Electronic address: goszczynski@iitd.pan.wroc.pl. 2. "Neolek" Laboratory of Biomedical Chemistry, Department of Experimental Oncology, Institute of Immunology and Experimental Therapy, PAS, 12 Rudolf Weigl St., 53-114 Wrocław, Poland. 3. Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology, PAS, 106 Lodowa St., 93-232 Łódź, Poland. Electronic address: zlesnikowski@cbm.pan.pl.
Abstract
BACKGROUND: Boron clusters represent a vast family of boron-rich compounds with extraordinary properties that provide the opportunity of exploitation in different areas of chemistry and biology. In addition, boron clusters are clinically used in boron neutron capture therapy (BNCT) of tumors. In this paper, a novel, in solid state (solvent free), thermal method for protein modification with boron clusters has been proposed. METHODS: The method is based on a cyclic ether ring opening in oxonium adduct of cyclic ether and a boron cluster with nucleophilic centers of the protein. Lysozyme was used as the model protein, and the physicochemical and biological properties of the obtained conjugates were characterized. RESULTS: The main residues of modification were identified as arginine-128 and threonine-51. No significant changes in the secondary or tertiary structures of the protein after tethering of the boron cluster were found using mass spectrometry and circular dichroism measurements. However, some changes in the intermolecular interactions and hydrodynamic and catalytic properties were observed. CONCLUSIONS: To the best of our knowledge, we have described the first example of an application of cyclic ether ring opening in the oxonium adducts of a boron cluster for protein modification. In addition, a distinctive feature of the proposed approach is performing the reaction in solid state and at elevated temperature. GENERAL SIGNIFICANCE: The proposed methodology provides a new route to protein modification with boron clusters and extends the range of innovative molecules available for biological and medical testing.
BACKGROUND:Boron clusters represent a vast family of boron-rich compounds with extraordinary properties that provide the opportunity of exploitation in different areas of chemistry and biology. In addition, boron clusters are clinically used in boron neutron capture therapy (BNCT) of tumors. In this paper, a novel, in solid state (solvent free), thermal method for protein modification with boron clusters has been proposed. METHODS: The method is based on a cyclic ether ring opening in oxonium adduct of cyclic ether and a boron cluster with nucleophilic centers of the protein. Lysozyme was used as the model protein, and the physicochemical and biological properties of the obtained conjugates were characterized. RESULTS: The main residues of modification were identified as arginine-128 and threonine-51. No significant changes in the secondary or tertiary structures of the protein after tethering of the boron cluster were found using mass spectrometry and circular dichroism measurements. However, some changes in the intermolecular interactions and hydrodynamic and catalytic properties were observed. CONCLUSIONS: To the best of our knowledge, we have described the first example of an application of cyclic ether ring opening in the oxonium adducts of a boron cluster for protein modification. In addition, a distinctive feature of the proposed approach is performing the reaction in solid state and at elevated temperature. GENERAL SIGNIFICANCE: The proposed methodology provides a new route to protein modification with boron clusters and extends the range of innovative molecules available for biological and medical testing.
Authors: Marcela A Garabalino; Nahuel Olaiz; Agustina Portu; Gisela Saint Martin; Silvia I Thorp; Emiliano C C Pozzi; Paula Curotto; María E Itoiz; Andrea Monti Hughes; Lucas L Colombo; David W Nigg; Verónica A Trivillin; Guillermo Marshall; Amanda E Schwint Journal: Radiat Environ Biophys Date: 2019-05-23 Impact factor: 1.925