DFG-Forschergruppe 630

Biologische Funktion von Organometallverbindungen
Biological function of organometallic compounds

Ergebnisse 2009

  • P.C. Kunz, W. Huber, A. Rojas, U. Schatzschneider, B. Spingler
    Manganese and rhenium tricarbonyl complexes of imidazol-based phosphane ligands: influence of the substitution pattern on the CO release properties
    Eur. J. Inorg. Chem. (2009) 5358-5366.
  • R. Bieda, I. Ott, R. Gust, W. S. Sheldrick
    Cytotoxic rhodium(III) polypyridyl complexes containing the tris(pyrazolyl)methane coligand: synthesis, DNA binding properties and structure-activity relationships
    Eur. J. Inorg. Chem. (2009) 3821-3831.
  • I. Ott, X. Qian, Y. Xu, D.H.W. Vlecken, I.J. Marques, D. Kubutat, J. Will, W. S. Sheldrick, P. Jesse, A. Prokop, C.P. Bagowski
    A Gold(I) Phosphine Complex Containing Naphthalimide Ligand Functions as a TrxR Inhibiting Antiproliferative Agent and Angiogenesis Inhibitor
    J. Med. Chem. 53 (2009) 763-770.
  • C. Walther, I. Ott, R. Gust, I. Neundorf
    Specific labeling with potent radiolabels alters the uptake of cell-penetrating peptides
    Biopolymers 92 (2009) 445-451.
  • R. Bieda, I. Ott, M. Dobroschke, A. Prokop, R. Gust, W. S. Sheldrick
    Structure-activity relationships and DNA binding properties of apoptosis inducing cytotoxic rhodium(III) polypyridyl complexes containing the cyclic thioether [9]aneS3
    J. Inorg. Biochem. 103 (2009) 698-708
  • M. Dobroschke, Y. Geldmacher, I. Ott, M. Harlos, L. Kater, L. Wagner, R. Gust, W. S. Sheldrick, A. Prokop
    Cytotoxic Rhodium(III) and Iridium(III) Polypyridyl Complexes: Structure-Activity Relationships, Antileukemic Activity and Apoptosis Induction
    ChemMedChem 4 (2009) 177-187.
  • J. Zagermann, K. Merz, N. Metzler-Nolte
    Labeling of Peptides with Halocarbonyltungsten Complexes Containing Functional eta(2)-Alkynyl Ligands
    Organometallics 28 (2009) 5090-5095.
  • J. Lemke, A. Pinto, P. Niehoff, V. Vasylyeva, N. Metzler-Nolte
    Synthesis, structural characterisation and anti-proliferative activity of NHC gold amino acid and peptide conjugates
    Dalton Trans. (2009) 7063-7070.
  • N. Hüsken, G. Gasser, S.D. Köster, N. Metzler-Nolte
    "Four-Potential" Ferrocene Labeling of PNA Oligomers via Click Chemistry
    Bioconjugate Chem. 20 (2009) 1578-1586.
  • A. Pinto, U. Hoffmanns, M. Ott, G. Fricker, N. Metzler-Nolte
    Modification with Organometallic Compounds Improves Crossing of the Blood-Brain Barrier of [Leu(5)]-Enkephalin Derivatives in an In Vitro Model System
    ChemBioChem 10 (2009) 1852-1860.
  • G. Gasser, O. Brosch, A. Ewers, T. Weyhermüller, N. Metzler-Nolte
    Synthesis and Characterisation of Hetero-Bimetallic Organometallic Phenylalanine and PNA Monomer Derivatives
    Dalton Trans. (2009) 4310-4317.
  • J. Zagermann, M.C. Kuchta, K. Merz, N. Metzler-Nolte
    Ruthenium-based bioconjugates: Synthesis and X-ray structure of the mixed ligand sandwich compound RuCpiPr(p-(CO2H)C6H4Tp) and labelling of amino acids and the neuropeptide enkephalin
    J. Organomet. Chem. 694 (2009) 862-867.
  • A. Gross, N. Metzler-Nolte
    Synthesis and Characterisation of a Ruthenocenoyl Bioconjugate with the Cyclic Octapeptide Octreotate
    J. Organomet. Chem. 694 (2009) 1185-1188.
  • G. Gasser, M.A. Neukamm, A. Ewers, O. Brosch, T. Weyhermüller, N. Metzler-Nolte
    Synthesis and Characterisation of Dicobalthexacarbonyl-Alkyne Amino Acid, Peptide and PNA Monomer Derivatives
    Inorg. Chem. 48 (2009) 3157-3166.
  • F. Noor, R. Kinscherf, G.A. Bonaterra, S. Walczak, S. Wölfl, N. Metzler-Nolte
    Enhanced Cellular Uptake and Cytotoxicity Studies of Organometallic Bioconjugates of the NLS Peptide in Hep G2 Cells
    ChemBioChem 10 (2009) 493-502.
  • I. Ott, X. Qian, Y. Xu, D. Kubutat, J. Will, W. S. Sheldrick, P. Jesse, A. Prokop, C. Bagowski
    A gold(I) phosphine complex containing naphthalimide ligand functions as a TrxR inhibiting antiproliferative agent and angiogenesis inhibitor
    J. Med. Chem. 52 (2009) 763-770.
  • O. Hohage, S. Manka, W. S. Sheldrick
    Downstream reaction of cisplatin with methionine-containing peptides: pH dependent competition between hydrolytic cleavage and macrochelation
    Inorg. Chim. Acta 362 (2009) 953-966.
  • A. Hunold, I. Neundorf, P. James, J. Neudörfl, H.-G. Schmalz
    Stereoselective Synthesis of new Ferrocene-derived Amino Acid Building Blocks
    Eur. J. Org. Chem. (2009) 4429-4440.
  • S. Seeberg (nee Kraft), C. Bischof, A. Loos, S. Braun, N. Jafarova, U. Schatzschneider
    A [4+2] mixed ligand approach to ruthenium DNA metallointercalators [Ru(tpa)(N-N)](PF6)2 using a tris(2-pyridylmethyl)amine (tpa) capping ligand
    J. Inorg. Biochem. 103 (2009) 1126-1134
  • A. Hille, I. Ott, A. Kitanovic, I. Kitanovic, H. Alborzina, E. Lederer, S. Wölfl, N. Metzler-Nolte, S. Schäfer, W.S. Sheldrick, C. Bischof, U. Schatzschneider, R. Gust
    [N,N'-Bis(salicylidene)-1,2-phenylenediamine]metal complexes with cell death promoting properties
    J. Biol. Inorg. Chem. 14, 711-725 (2009)
  • H. Pfeiffer, A. Rojas, J. Niesel, U. Schatzschneider
    Sonogashira and "Click" reactions in the N-terminal and side chain functionalization of peptides with [Mn(CO)3(tpm)]+-based CO releasing molecules (tpm = tris(pyrazolyl)methane)
    Dalton Trans. 4292-4298 (2009)
  • H.W. Peindy N'Dongo, I. Ott, R. Gust, U. Schatzschneider
    Microwave-assisted solid-phase synthesis, cellular uptake, and cytotoxicity studies of cymantrene-peptide bioconjugates
    J. Organomet. Chem. 694 (2009) 823-827
  • I. Ott, B. Kircher, C.P. Bagowski, D.H.W. Vlecken, E.B. Ott, J. Will, K. Bensdorf, W. S. Sheldrick, R. Gust
    Modulation of the Biological Properties of Aspirin by Bioorganometallic Derivatisation
    Angew. Chem. Int. Ed. 48 (2009) 1160-1163.

Ergebnisse 2008

  • M. Schlenk, I. Ott, R. Gust
    Cobalt-Alkyne Complexes with Imidazoline Ligands as Estrogenic Carriers: Synthesis and Pharmacological Investigations
    J. Med. Chem. 51 (2008) 7318-7322.
  • C. Walther, K. Meyer, R. Rennert, I. Neundorf
    Quantum Dot-Carrier Peptide Conjugates Suitable for Imaging and Delivery Applications
    Bioconjugate Chem. 19 (2008)2346-2356.
  • J. Will, D. Wolters, W. S. Sheldrick
    Characterisation of Cisplatin Binding Sites in Human Serum Proteins using Hyphenated Multidimensional Liquid Chromatography and ESI Tandem Mass Spectrometry
    ChemMedChem. 3 (2008) 1696 - 1707.
  • M. A. Scharwitz, I. Ott, Y. Geldmacher, R. Gust, W. S. Sheldrick
    Cytotoxic half-sandwich rhodium(III) complexes: polypyridyl ligand influence on their DNA binding properties and cellular uptake
    J. Organomet. Chem. 693 (2008) 2299 - 2309.
  • M. A. Scharwitz, I. Ott, R. Gust, A. Kromm, W. S. Sheldrick
    Synthesis, cellular uptake and structure-activity relationships for potent cytotoxic trichlorididoiridium(III) polypyridyl complexes
    J. Inorg. Biochem. 102 (2008) 1623 - 1630.
  • I. Ott, M. Scharwitz, H. Scheffler, W. S. Sheldrick, R. Gust
    Atomic absorption spectrometric determination of the iridium content of tumor cells exposed to an iridium metallodrug
    J. Pharm. Biomed. Anal. 47 (2008) 938 - 942.
  • O. Hohage, S. Manka, W. S. Sheldrick
    Downstream reaction of cisplatin with methionine-containing peptides: pH dependent competition between hydrolytic cleavage and macrochelation
    Inorg. Chim. Acta, doi: 10.1016/j.ica.2008.01.011
  • S.D. Köster, J. Dittrich, G. Gasser, N. Hüsken, I.C. Henao Castaneda, J.L. Jios, C.O. Della Vedova, N. Metzler-Nolte
    Spectroscopic and Electrochemical Studies of Ferrocenoyl Triazole Amino Acid and Peptide Bioconjugates Synthesized by Click Chemistry
    Organometallics 27 (2008) 6326-6332
  • I. Neundorf, J. Hoyer, K. Splith, R. Rennert, H.W. Peindy N'Dongo, U. Schatzschneider
    Cymantrene conjugation modulates the intracellular distribution and induces high cytotoxicity of a cell-penetrating peptide
    Chem. Commun. (2008) 5604-5606
  • H.W. Peindy N'Dongo, I. Neundorf, K. Merz, U. Schatzschneider
    Synthesis, characterization, and X-ray crystallography of cymantrene keto carboxylic acids for IR labelling of bioactive peptides on a solid support
    J. Inorg. Biochem. 102 (2008) 2114-2119
  • M. Harlos, I. Ott, R. Gust, H. Alborzinia, S. Wölfl, A. Kromm, W. S. Sheldrick
    Synthesis, biological activity and structure activity relationships for potent cytotoxic rhodium (III) polypyridyl complexes
    J. Med. Chem. 51 (2008) 3924-3933
  • D. Zwanziger, A. G. Beck-Sickinger
    Radiometal Targeted Tumor Diagnosis and Therapy with Peptide Hormones
    Curr. Pharm. Design 14 (2008) 2385-2400
  • D. Zwanziger, I. U. Khan, I. Neundorf, S. Sieger, L. Lehmann, M. Friebe, L. Dinkelborg, A. G. Beck-Sickinger
    Novel Chemically Modified Analogues of Neuropeptide Y (NPY) for Tumour Targeting
    Bioconjugate Chem. 19 (2008) 1430-1438
  • A. Gansäuer, I. Winkler, D. Worgull, T. Lauterbach, D. Franke, A. Selig, L. Wagner, A. Prokop
    Carbonyl-Substituted Titanocenes: A Novel Class of Cytostatic Compounds with High Antitumor and Antileukemic Activity
    Chem. Eur. J. 14 (2008) 4160-4163
  • I. Neundorf, R. Rennert, J. Franke, I. Közle, R. Bergmann
    Detailed Analysis Concerning the Biodistribution and Metabolism of Human Calcitonin-Derived Cell-Penetrating Peptides
    Bioconjugate Chem. 19 (2008) 1596-1603
  • J. Lemke, N. Metzler-Nolte
    The Synthesis of Ruthenium and Rhodium Complexes with Functionalized N-Heterocyclic Carbenes and Their Use in Solid Phase Peptide Synthesis
    Eur. J. Inorg. Chem. (2008) 3359?366
  • G. Gasser, N. Hüsken, S.D. Köster, N. Metzler-Nolte
    Synthesis of organometalic PNA oligomers by click chemistry
    Chem. Comm. (2008) 3675-3677
  • U. Schatzschneider, J. Niesel, I. Ott, R. Gust, H. Alborzinia, S. Wölfl
    Cellular Uptake, Cytotoxicity, and Metabolic Profiling of Ruthenium(II) Polypyridyl Complexes [Ru(bpy)2(N-N)]Cl2 with N-N = bpy, phen, dpq, dppz, and dppn
    ChemMedChem 3 (2008) 1104-1109
  • O. I. Ornatsky, X. Lou, M. Nitz, S. Schäfer, W. S. Sheldrick, V. I. Baranov, D. R. Bandura, S. D. Tanner
    Measurements of antigens and intracellular DNA by detection of elemental tags and metallointercalators using inductively coupled plasma mass spectrometry
    Anal. Chem. 80 (2008) 2539-2547
  • J. Will, W. S. Sheldrick, D. Wolters
    Characterisation of cisplatin coordination sites in cellular E. coli DNA binding proteins by combined biphasic liquid chromatography and ESI tandem mass spectrometry
    J. Biol. Inorg. Chem. 13 (2008) 421-434
  • S. I. Kirin, I. Ott, R. Gust, W. Mier, T. Weyhermüller, N. Metzler-Nolte
    Cellular uptake quantification of metallated peptide and peptide nucleic acid bioconjugates by atomic absorption spectroscopy
    Angew. Chem. Int. Ed. (2008), 47, 955-959; Angew. Chem. (2008), 120, 969-973
  • C. D.Sergeant, I. Ott, A. Sniady, S. Meneni, R. Gust, A. L. Rheingold, R. Dembinski
    Metallo-nucleosides: synthesis and biological evaluation of hexacarbonyl dicobalt 5-alkynyl-2'-deoxyuridines
    Org. Biomol. Chem. 6 (2008) 73-80
  • I. Ott, B. Kircher, R Dembinski., R. Gust
    Alkyne hexacarbonyl dicobalt complexes in medicinal chemistry and drug development
    Expert Opin. Therap. Patents 18 (2008) 327-337
  • T. Kapp, M. Krüger, I. Ott, S. Steiner, P. Schumacher, D. Nachbaur, G. Gastl, R. Gust, B. Kircher
    Biological effect of mono- and dinuclear alkylamine platinum(II) compounds on human lymphoma cells
    J. Inorg. Biochem. 102 (2008) 713-720
  • R. Rennert, I. Neundorf, H. Jahnke, P. Suchowerskyj, P. Dournaud, A. Robitzki, A. G. Beck-Sickinger
    Generation of carrier peptides for the delivery of nucleic acid drugs in primary cells
    ChemMedChem 3 (2008) 241-253
  • I. U. Khan, A. G. Beck-Sickinger
    Targeted Tumor Diagnosis and Therapy with Peptide Hormones as Radiopharmaceuticals, Anti-Cancer Agents
    Med. Chem. 8 (2008) 186-199
  • J. Niesel, A. Pinto, H.W. Peindy N'Dongo, K. Merz, I. Ott, R. Gust, U. Schatzschneider
    Photoinduced CO release, cellular uptake, and cytotoxicity of a tris(pyrazolyl)methane manganese tricarbonyl complex
    Chem. Commun. (2008) 1798-1800
  • M. Neukamm, A. Pinto, N. Metzler-Nolte
    Synthesis and cytotoxicity of a cobaltcarbonyl-alkyne enkephalin bioconjugate
    Chem. Commun. (2008) 232

Ergebnisse 2007

  • A. Pfletschinger, U. Schneider, J. Lex, H.-G. Schmalz
    Stereospecific Side Chain Activation in Cyclobutadiene-Fe(CO)3 Chemistry: A Theoretical and Experimental Study on the Structure and Configurational Stability of Cationic, Radical and Anionic Intermediates
    Eur. J. Org. Chem. (2007) 3991-3998
  • I. Ott, H. Scheffler, R. Gust
    Development of a method for the quantification of the molar gold concentration in tumor cells exposed to gold containing drugs
    ChemMedChem 2 (2007) 702-707
  • S. I. Kirin, T. Weyhermüller, K. Merz, N. Metzler-Nolte
    The x-ray single crystal structures of an acid-functionalized bis(2-picolyl)amine (bpa) ligand with Palladium(II) and Zinc(II) display different intermoleclar interactions around the common (H2O)2anion2 motif
    Z. Anorg. Allg. Chem. 633 (2007) 2706
  • E. G. Garayoa, G. Schweinsberg, V. Maes, D. Rüegg, A. Blanc, P. Bläuenstein, D. A. Tourwé, A. G. Beck-Sickinger, P. A. Schubiger
    New[99mTc] bombesin analogues with improved biodistribution for targeting gastrin releasing-peptide receptor-positive tumors
    J. Nucl. Med. Mol. Imaging 51 (2007) 42-50
  • I. U. Khan, R. Reppich, A. G. Beck-Sickinger
    Identification of Neuropeptide Y Cleavage Products in Human Blood to Improve Metabolic Stability
    Biopolymers 88 (2007) 182-189
  • M. C. Kuchta, A. Gross, A. Pinto, N. Metzler-Nolte
    Labeling of the neuropeptide enkephalin with functionalized Tris (pyrazolyl)borate complexes: Solid-phase synthesis and characterization of p-[Enk-OH]COC6H4TpPtMe3 and p-[Enk-OH]COC6H4Tp(Me)Re(CO)3
    Inorg. Chem. 46 (2007) 9400
  • J. L. Jios, S. I. Kirin, N. N. Buceta, T. Weyhermüller, C. O. Della Vedova, N. Metzler-Nolte
    Synthesis and structural characterization of metallated bioconjugates: C-terminal labeling of amino acids with aminoferrocene
    J. Organomet. Chem. 692 (2007) 4209
  • J. Caddy, U. Hoffmanns, N. Metzler-Nolte
    Introduction of phosphine-gold(I) precursors into a Cys-modified enkephalin neuropeptide as part of solid phase peptide synthesis
    Z. Naturforsch. B 62 (2007) 460
  • E. Garcia Garayoa, D. Ruegg, P. Blauenstein, M. Zwimpfer, I. U. Khan, V. Maes, A. Blanc, A. G. Beck-Sickinger, D. A. Tourwe, P. A. Schubiger
    Chemical and biological characterization of new Re(CO)3/[99mTc](CO)3 bombesin analogues
    Nucl. Med. Biol. 34 (2007) 17-28
  • R. Gust, Ingo Ott
    Non-platinum metal complexes as anti-cancer drugs
    Arch. Pharm. 340 (2007) 117-126
  • M. C. Kuchta, C. Gemel, N. Metzler-Nolte
    An amino acid bioconjugate of an organoplatinum tris(pyrazolyl)borate complex: Synthesis and structure of
    [p-(tBuO-Phe-CO)C6H3Tp]PtMe3
    J. Organomet. Chem. 692 (2007) 1310-1314
  • J. Will, A. Kyas, W. S. Sheldrick, D. Wolters
    Identification of (η6-arene) ruthenium(II) protein binding sites in E-coli cells by combined multidimensional liquid chromatography and ESI tandem mass spectrometry: specific binding of [(η6-p-cymene)RuCl2(DMSO)] to stress-regulated proteins and to helicases
    J. Biol. Inorg. Chem. 12 (2007) 883
  • R. Gust, Ingo Ott
    Preclinical and clinical studies on the use of platinum complexes for breast cancer treatment
    Anti-Cancer Agents in Medicinal Chemistry 7 (2007) 95-110
  • F. Pluder, A. G. Beck-Sickinger
    One-step procedure for staining of proteins with ruthenium II tris (bathophenanthroline disulfonate)
    J. Anal. Biochem. 361 (2007) 299-301
  • S. Schäfer, I. Ott, R. Gust, W. S. Sheldrick
    Influence of the polypyridyl (pp) ligand size on the DNA binding properties, cytotoxicity and cellular uptake of organoruthenium(II) complexes of the type [(η6-C6Me6)Ru(L)(pp)]n+ [L = Cl, n=1; L = (NH2)2CS, n=2]
    Eur. J. Inorg. Chem. (2007) 3034-3046
  • S. Schäfer and W. S. Sheldrick
    Coligand tuning of the DNA binding properties of half-sandwich organometallic intercalators: Influence of polypyridyl (pp) and monodentate ligands (L = Cl, (NH2)2CS, (NMe2)2CS) on the intercalation of (η-5-pentamethylcyclopentadienyl)-iridium(III)- dipyridoquinoxaline and -dipyridophenazine complexes
    J. Organomet. Chem. 692 (2007) 1300-1309
  • S. Schertl, R. Hartmann, C. Batzl-Hartmann, T. Spruß, A. Maucher, E. von Angerer, C. Schiller, M. Schneider, R. Gust, H. Schönenberger
    Platinum(II) complexes interfering with testicular steroid biosynthesis: drugs for the therapy of advanced or recurrent prostate cancers? Preclinical studies
    J. Cancer Res. Clin. Oncol. 133 (2007) 153-167

Ergebnisse 2006

  • I. Ott, A. Abraham, P. Schumacher, H. Shorafa, G. Gastl, R. Gust, B. Kircher
    Synergistic and additive antiproliferative effects on human leukemia cell lines induced by combining acetylenehexacarbonyldicobalt complexes with the tyrosine kinase inhibitor imatinib
    J. Inorg. Biochem. 100 (2006) 1903-19063
  • I. Ott, R. Gust
    Medizinische Chemie der Platinkomplexe. (written in German)
    Pharm. Unserer Zeit 35 (2006) 124-133
  • T. Kapp, S. Müller, R. Gust
    Dinuclear alkylamine platinum (II) complexes of [1,2-bis-(4-fluorophenyl)ethylenediamine platinum(II): influence of endocytosis and copper and organic cation transporter systems on cellular uptake
    ChemMedChem 1 (2006) 560-564
  • A. Dullin, F. Dufrasne, M. Gelbcke, R. Gust
    Synthesis and cytotoxicity of enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)-3-methylbutane]platinum(II) complexes
    ChemMedChem 1 (2006) 644-653
  • T. Kapp, A. Dullin, R. Gust
    Mono- and polynuclear [alkylamine]platinum(II) complexes of [1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II): synthesis and investigations on cytotoxicity, cellular distribution, and DNA and protein binding
    J. Med. Chem. 49 (2006) 1182-1190
  • L. Barisic, V. Rapic, N. Metzler-Nolte
    Incorporation of the unnatural organometallic amino acid 1'-aminoferrocene-1-carboxylic acid (Fca) into oligopeptides by a combination of Fmoc and Boc solid phase synthetic methods
    Eur. J. Inorg. Chem. (2006) 4019-4021
  • N. Metzler-Nolte
    Medizinische Organometallchemie
    Nachr. Chem. 54 (2006) 966-970
  • P. James, J. Neudörfl, M. Eissmann, P. Jesse, A. Prokop, H.-G. Schmalz
    Enantioselective Synthesis of Ferrocenyl Nucleoside Analogues with Apoptosis-Inducing Activity
    Org. Lett. 8 (2006) 2763-2766
  • U. Schatzschneider, N. Metzler-Nolte
    New emerging principles in medicinal organometallic chemistry
    Angew. Chem. 118 (2006) 1534-1537
  • S.I. Kirin, U. Schatzschneider, X. de Hatten, T. Weyhermüller, N. Metzler-Nolte
    1,n'-Disubstituted ferrocenoyl amino acids and dipeptides: Conformational analysis by CD spectroscopy, X-ray crystallography, and DFT calculations
    J. Organomet. Chem. 691 (2006) 3451-3457
  • I. Ott, R. Gust
    Anomaly of inorganic cytostatic drugs. Medical chemistry of platinum complexes
    Pharmazie in unserer Zeit 35 (2006) 124-133
  • U. Hoffmanns, N. Metzler-Nolte
    Use of the Sonogashira Coupling Reaction for the "Two-Step" Labeling of Phenylalanine Peptide Side Chains with Organometallic Compounds
    Bioconjugate Chem. 17 (2006) 204-213
  • S. I. Kirin, H. B. Kraatz, N. Metzler-Nolte
    Systematizing structural motifs and nomenclature in 1,N'-disubstituted ferrocene peptides
    Chem. Soc. Rev. 35 (2006) 348-354
  • O. Hohage, W. S. Sheldrick
    Cisplatin mediates selective downstream hydrolytic cleavage of Met-(Gly)n-His segments (n =1,2) in methionine- and histidine-containing peptides: The role of ammine loss trans to the initial Pt-S(Met) anchor in facilitating amide hydrolysis
    J. Inorg. Biochem. 100 (2006) 1506-1513