title: Synthesis and active oxygen generation by new emodin derivatives and their gonadotropin-releasing hormone conjugates.
abstract: In an attempt to develop efficient chemotherapeutic agents targeted at malignant cells that express receptors, we synthesized five new emodin derivatives and their gonadotropin-releasing hormone (GnRH) conjugates to be used as potential photoactive conjugates. Emodin was modified at its hydroxy groups and included different spacers for conjugation of the peptide. We used electron spin resonance (ESR) and spin trapping techniques to study the light-stimulated redox properties of the emodin derivatives and their GnRH conjugates. Upon irradiation, all new emodin derivatives and their conjugates stimulated the formation of singlet oxygen, that is, (1)O(2), and oxygen radicals, that is, O(2)(-)(*) and OH(*). However, substantial differences were found between the tested derivatives as to the efficacy of reactive oxygen species (ROS) production. Because of its superior ROS production properties, [d-Lys(6)(MeoEmo)]GnRH was selected as a leading conjugate. En-route to evaluate its targeting capacity, this potentially cytotoxic conjugate was tested in vitro to determine its hormonal activity and binding affinity to GnRH receptors.
authors.affiliation: Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Lev-Goldman
authors.forename: Brenda
authors.initials: B
authors.lastname: Mester
authors.forename: Nurit
authors.initials: N
authors.lastname: Ben-Aroya
authors.forename: Yitzhak
authors.initials: Y
authors.lastname: Koch
authors.forename: Lev
authors.initials: L
authors.lastname: Weiner
authors.forename: Mati
authors.initials: M
authors.lastname: Fridkin
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004578:Electron Spin Resonance Spectroscopy; D004642:Emodin / Q000737:chemistry*; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010100:Oxygen / Q000737:chemistry*; D011966:Receptors, LHRH / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D004642:Emodin; D010100:Oxygen