title: In vitro cytotoxic effect of difluoromethylomithine increased nonspecifically by peptide coupling.
abstract: Difluoromethylomithine (DFMO)-peptide conjugates were synthesized as prodrugs to improve the cytotoxic efficacy of DFMO. All conjugates inhibited cell growth in different cell lines more effectively than DFMO itself. The best cytotoxic effect was achieved in all cell lines by DFMO-Glu-His-Phe-Arg-Trp-Gly-OMe, where the carrier peptide is a melanotropin hormone fragment. Although this conjugate is capable of displacing labeled melanotropin from its receptor, its cytotoxic effect on the receptor-positive human melanoma cell line has not been proven to be receptor-mediated. The differences in the cytotoxicities of the congeners seem to be influenced, at least in part, by the nature of the carrier molecule.
authors.affiliation: Research Group for Peptide Chemistry, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: H
authors.initials: H
authors.lastname: Süli-Vargha
authors.forename: R
authors.initials: R
authors.lastname: Morandini
authors.forename: J
authors.initials: J
authors.lastname: Bódi
authors.forename: L
authors.initials: L
authors.lastname: Nagy
authors.forename: H
authors.initials: H
authors.lastname: Medzihradszky-Schweiger
authors.forename: G
authors.initials: G
authors.lastname: Ghanem
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity*; D000518:Eflornithine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D006868:Hydrolysis; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000633:toxicity; D011979:Receptors, Pituitary Hormone / Q000096:biosynthesis / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D011979:Receptors, Pituitary Hormone; C029446:MSH receptor; D009074:Melanocyte-Stimulating Hormones; D013936:Thymidine; D000518:Eflornithine