title: Lamellarin D bioconjugates II: Synthesis and cellular internalization of dendrimer and nuclear location signal derivatives.
abstract: The design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4- to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines (MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3 and 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed, and a nuclear distribution pattern was observed for 4, which contains a nuclear localization signaling sequence.
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park-University of Barcelona, Baldiri Reixac 10, E-08028 Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pla
authors.forename: Marc
authors.initials: M
authors.lastname: Martí
authors.forename: Josep
authors.initials: J
authors.lastname: Farrera-Sinfreu
authors.forename: Daniel
authors.initials: D
authors.lastname: Pulido
authors.forename: Andrés
authors.initials: A
authors.lastname: Francesch
authors.forename: Pilar
authors.initials: P
authors.lastname: Calvo
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas
authors.forename: Miriam
authors.initials: M
authors.lastname: Royo
authors.forename: Rosa
authors.initials: R
authors.lastname: Aligué
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Mercedes
authors.initials: M
authors.lastname: Alvarez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D019913:Nuclear Localization Signals / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D050091:Dendrimers; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; D019913:Nuclear Localization Signals; C455554:lamellarin D; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols; D004264:DNA Topoisomerases, Type I