title: Synthesis and properties of cell-targeted Zn(II)-phthalocyanine-peptide conjugates.
abstract: Two Zn-Pc-peptide conjugates bearing either a short linker or a long PEG-linker between the macrocycle and a bifunctional peptide containing the nucleoplasmin and HIV-1 Tat 48-60 sequences have been synthesized in order to increase the Pc cell-targeting ability and to evaluate the effect of the linker. The presence of the peptide chain increased the water solubility of the Pc macrocycle and, consequently, its fluorescence in aqueous solutions. The highest fluorescence quantum yields were observed at low pH (5.0) for both conjugates and were always higher for the conjugate bearing the short linker. Both conjugates were found to have low dark cytotoxicity toward human HEp2 cells (IC50 > 77 microM) but were highly phototoxic (IC50 < 2 microM at 1 J cm-2). The conjugate bearing the long PEG-linker accumulated the most within cells (26 times more than the unconjugated Zn-Pc), followed by the short linker conjugate (17 times more than the unconjugated Zn-Pc). Both conjugates were found to localized preferentially within the cell lysosomes.
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Sibrian-Vazquez
authors.forename: Javier
authors.initials: J
authors.lastname: Ortiz
authors.forename: Irina V
authors.initials: IV
authors.lastname: Nesterova
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernandez-Lazaro
authors.forename: Angela
authors.initials: A
authors.lastname: Sastre-Santos
authors.forename: Steven A
authors.initials: SA
authors.lastname: Soper
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015032:Zinc / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D015032:Zinc; C013647:phthalocyanine