title: Internalization and stability of a thymidylate synthase Peptide inhibitor in ovarian cancer cells.
abstract: Information on the cellular internalization and stability of the ovarian cancer cell growth inhibitor peptide, LSCQLYQR (LR), is vital for lead optimization. Ad-hoc-synthesized LR/fluorescent-probe conjugates were used to monitor the internalization of the peptide. Mass spectrometry was used to identify adducts resulting from the thiol reactivity of the cysteine residue in LR. A mechanistic model is proposed to explain the observed change in intracellular peptide amount over time. Structural modifications can be foreseen to improve the peptide stability.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia , Via Campi 183, 41125 Modena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cannazza
authors.forename: Addolorata Stefania
authors.initials: AS
authors.lastname: Cazzato
authors.forename: Chiara
authors.initials: C
authors.lastname: Marraccini
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pavesi
authors.forename: Silvia
authors.initials: S
authors.lastname: Pirondi
authors.forename: Remo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Michela
authors.initials: M
authors.lastname: Pelà
authors.forename: Chiara
authors.initials: C
authors.lastname: Frassineti
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.forename: Gaetano
authors.initials: G
authors.lastname: Marverti
authors.forename: Glauco
authors.initials: G
authors.lastname: Ponterini
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Costi
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D005453:Fluorescence; D006801:Humans; D018613:Microscopy, Confocal; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D013940:Thymidylate Synthase