title: Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.
abstract: To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc , 17. listopadu 1192/12, 771 46 Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Soural
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc , 17. listopadu 1192/12, 771 46 Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Hodon
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc , 17. listopadu 1192/12, 771 46 Olomouc, Czech Republic.
authors.forename: Niall J
authors.initials: NJ
authors.lastname: Dickinson
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc , 17. listopadu 1192/12, 771 46 Olomouc, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Sidova
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Sona
authors.initials: S
authors.lastname: Gurska
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Dzubak
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Marian
authors.initials: M
authors.lastname: Hajduch
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Sarek
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Palacky University in Olomouc , 17. listopadu 1192/12, 771 46 Olomouc, Czech Republic.|Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc , Hnevotinska 5, 779 00 Olomouc, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Urban
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001710:Biotin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019921:Biotinylation; D045744:Cell Line, Tumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D060327:Solid-Phase Synthesis Techniques; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes
chemical_list: D000970:Antineoplastic Agents; D001710:Biotin; D014315:Triterpenes; C480546:lupane; D053978:Pentacyclic Triterpenes