title: Synthesis of novel, peptidic kinase inhibitors with cytostatic/cytotoxic activity.
abstract: The utility of a novel, chemoenzymatic procedure for the stereocontrolled synthesis of small peptides is presented in the preparation and structure optimisation of dipeptides with cytostatic/cytotoxic activity. The method uses Passerini multicomponent reaction for the preparation of racemic scaffold which is then enantioselectively hydrolysed by hydrolytic enzymes. Products of these transformations are further functionalised towards title compounds. Both activity and selectivity towards tumor cells is optimised. Final compound is shown to be an inhibitor of the protein kinase signaling pathway.
authors: Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland.
authors: Wiktor
authors: W
authors: Szymanski
authors: Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland.
authors: Magdalena
authors: M
authors: Zwolinska
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors: Szymon
authors: S
authors: Klossowski
authors: Department of Histology and Embryology, The Medical University of Warsaw, 5 Chalubinskiego Str., 02-004 Warsaw, Poland.
authors: Izabela
authors: I
authors: Młynarczuk-Biały
authors: Department of Histology and Embryology, The Medical University of Warsaw, 5 Chalubinskiego Str., 02-004 Warsaw, Poland.
authors: Lukasz
authors: L
authors: Biały
authors: Department of Immunology, The Medical university of Warsaw, 5 Chalubinskiego Str., 02-004 Warsaw, Poland.
authors: Tadeusz
authors: T
authors: Issat
authors: Department of Histology and Embryology, The Medical University of Warsaw, 5 Chalubinskiego Str., 02-004 Warsaw, Poland.
authors: Jacek
authors: J
authors: Malejczyk
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland. Electronic address: rysza@icho.edu.pl.
authors: Ryszard
authors: R
authors: Ostaszewski
mesh_terms: D054697:Cytostatic Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000138:chemical synthesis*; D006801:Humans; D015394:Molecular Structure; D057786:Peptidomimetics / Q000138:chemical synthesis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D054697:Cytostatic Agents; D004151:Dipeptides; D057786:Peptidomimetics; D047428:Protein Kinase Inhibitors
keywords: Biotransformations; Cytostatic/cytotoxic effect; Kinase inhibitors; Peptidomimetics