Hauptinhalt

Publikationen

2024

Maluck, S.; Bobrovsky, R.; Poór, M.; Lange, R.W.; Steinmetzer, T.; Jerzsele, Á.; Adorján, A.; Bajusz, D.; Rácz, A.; Pászti-Gere, E. In Vitro Evaluation of Antipseudomonal Activity and Safety Profile of Peptidomimetic Furin Inhibitors. Biomedicines 2024, 12, 2075.

Brands J, Bravo S, Jürgenliemke L, Grätz L, Schihada H, Frechen F, Alenfelder J, Pfeil C, Ohse PG, Hiratsuka S, Kawakami K, Schmacke LC, Heycke N, Inoue A, König G, Pfeifer A, Wachten D, Schulte G, Steinmetzer T, Watts VJ, Gomeza J, Simon K, Kostenis E. A molecular mechanism to diversify Ca2+ signaling downstream of Gs protein-coupled receptors. Nat. Commun. 2024, 15, 7684.

Wiedemeyer SJA, Wu G, Lang-Henkel H, Whisstock JC, Law RHP, Steinmetzer T. Macrocyclic inhibitors targeting the prime site of the fibrinolytic serine protease plasmin. ChemMedChem. 2024, 19, e202400360.

Huber S, Braun NJ, Schmacke LC, Murra R, Bender D, Hildt E, Heine A, Steinmetzer T. Synthesis and structural characterization of new macrocyclic inhibitors of the Zika virus NS2B-NS3 protease. Arch Pharm. 2024, 357, e2400250.

Bestle D, Bittel L, Werner AD, Kämper L, Dolnik O, Krähling V, Steinmetzer T, Böttcher-Friebertshäuser E. Novel proteolytic activation of Ebolavirus glycoprotein GP by TMPRSS2 and cathepsin L at an uncharted position can compensate for furin cleavage. Virus Res. 2024, 347, 199430.

Gamba D, van Eijk N, Lányi K, Monostory K, Steinmetzer T, Marosi A, Rácz A, Bajusz D, Kruhl D, Böttcher-Friebertshäuser E, Pászti-Gere E. PK/PD investigation of antiviral host matriptase/TMPRSS2 inhibitors in cell models. Sci Rep. 2024, 14, 16621.

van Niekerk A. A.; Maluck S., Mag P., Kővágó C., Kerek Á., Jerzsele Á., Steinmetzer T., Pászti-Gere E. Antiviral Drug Candidate Repositioning for Streptococcus suis Infection in Non-Tumorigenic Cell Models. Biomedicines 2024, 12, 783.

M. R. Heindl, A. L. Rupp, M. Schwerdtner, D. Bestle, A. Harbig, A. De Rocher, L. C. Schmacke, B. Staker, T. Steinmetzer, D. A. Stein, H. M. Moulton, E. Böttcher-Friebertshäuser, ACE2 acts as a novel regulator of TMPRSS2-catalyzed proteolytic activation of influenza A virus in airway cells. J. Virol., 2024, 98, e0010224.

 Lange, R. W.; Bloch, K.; Heindl, M. R.; Wollenhaupt, J.; Weiss, M. S.; Brandstetter, H.; Klebe, G.; Falcone, F. H.; Böttcher-Friebertshäuser, E.; Dahms, S. O.; Steinmetzer, T., Fragment-Based Design, Synthesis, and Characterization of Aminoisoindole-Derived Furin Inhibitors. ChemMedChem 2024, 19, e202400057.

2023

Wiedemeyer, S. J. A.; Wu, G.; Pham, T. L. P.; Lang-Henkel, H.; Perez Urzua, B.; Whisstock, J. C.; Law, R. H. P.; Steinmetzer, T., Synthesis and Structural Characterization of Macrocyclic Plasmin Inhibitors. ChemMedChem 2023, 18, e202200632.

van Eijk, N.; Schmacke, L. C.; Steinmetzer, T.; Pilgram, O.; Poór, M.; Pászti-Gere, E., In vitro testing of host-targeting small molecule antiviral matriptase/TMPRSS2 inhibitors in 2D and 3D cell-based assays. Biomed Pharmacother 2023, 168, 115761.

Lányi, K.; Monostory, K.; Steinmetzer, T.; Jerzsele, Á.; Pászti-Gere, E., In Vitro Pharmacokinetic Behavior of Antiviral 3-Amidinophenylalanine Derivatives in Rat, Dog and Monkey Hepatocytes. Biomedicines 2023, 11, 682.

Braun, N. J.; Huber, S.; Schmacke, L. C.; Heine, A.; Steinmetzer, T., Boroleucine-Derived Covalent Inhibitors of the ZIKV Protease. ChemMedChem 2023, 18, e202200336.

Hammerschmidt, S. J.; Huber, S.; Braun, N. J.; Lander, M.; Steinmetzer, T.; Kersten, C., Thermodynamic characterization of a macrocyclic Zika virus NS2B/NS3 protease inhibitor and its acyclic analogs. Arch Pharm (Weinheim) 2023, 356, e2200518.

2022

Huber, S.; Braun, N. J.; Schmacke, L. C.; Quek, J. P.; Murra, R.; Bender, D.; Hildt, E.; Luo, D.; Heine, A.; Steinmetzer, T., Structure-Based Optimization and Characterization of Macrocyclic Zika Virus NS2B-NS3 Protease Inhibitors. J. Med. Chem. 2022, 65 (9), 6555-6572.

Fedor, Z.; Szentkirályi-Tóth, A.; Nagy, G.; Szimrók, Z.; Varga, E.; Pászti, A.; Pászti, Z.; Jerzsele, Á.; Pilgram, O.; Steinmetzer, T.; Mátis, G.; Neogrády, Z.; Pászti-Gere, E., Interspecies Comparisons of the Effects of Potential Antiviral 3-Amidinophenylalanine Derivatives on Cytochrome P450 1A2 Isoenzyme. Vet. Sci. 2022, 9, 156.

Lam van, T. V.; Ivanova, T.; Lindberg, I.; Böttcher-Friebertshäuser, E.; Steinmetzer, T.; Hardes, K., Design, synthesis, and characterization of novel fluorogenic substrates of the proprotein convertases furin, PC1/3, PC2, PC5/6, and PC7. Anal. Biochem. 2022, 655, 114836.

Pászti-Gere, E.; Szentkirályi, A.; Fedor, Z.; Nagy, G.; Szimrók, Z.; Pászti, Z.; Pászti, A.; Pilgram, O.; Steinmetzer, T.; Bodnárová, S.; Fliszár-Nyúl, E.; Poór, M., In vitro interaction of potential antiviral TMPRSS2 inhibitors with human serum albumin and cytochrome P 450 isoenzymes. Biomed. Pharmacother. 2022, 146, 112513.

Pilgram, O.; Keils, A.; Benary, G. E.; Müller, J.; Merkl, S.; Ngaha, S.; Huber, S.; Chevillard, F.; Harbig, A.; Magdolen, V.; Heine, A.; Böttcher-Friebertshäuser, E.; Steinmetzer, T., Improving the selectivity of 3-amidinophenylalanine-derived matriptase inhibitors. Eur. J. Med. Chem. 2022, 238, 114437.

Pászti-Gere, E.; Szentkirályi-Tóth, A.; Szabó, P.; Steinmetzer, T.; Fliszár-Nyúl, E.; Poór, M., In vitro characterization of the furin inhibitor MI-1851: Albumin binding, interaction with cytochrome P450 enzymes and cytotoxicity. Biomed. Pharmacother. 2022, 151, 113124.

Umbach, S.; Levin, R.; Neumann, S.; Steinmetzer, T.; Dötsch, V.; Bernhard, F., Transfer mechanism of cell-free synthesized membrane proteins into mammalian cells. Front. Bioeng. Biotechnol. 2022, 10, 906295.

2021

Dahms, S. O., Haider, T., Klebe, G., Steinmetzer, T., Brandstetter, H. OFF-State-Specific Inhibition of the Proprotein Convertase Furin. ACS Chem Biol 2021, 16, 1692-1700.

Schencking, I., Schäfer, E. M., Scanlan, J. H. W., Wenzel, B. M., Emmerich, R. E., Steinmetzer, T., Diederich, W. E., Schlitzer, M., Hartmann, R. K. RNase P Inhibitors Identified as Aggregators. Antimicrob Agents Chemother 2021, 65, e0030021.

Lam van, T. V., Heindl, M. R., Schlutt, C., Böttcher-Friebertshäuser, E., Bartenschlager, R., Klebe, G., Brandstetter, H., Dahms, S. O., Steinmetzer, T. The Basicity Makes the Difference: Improved Canavanine-Derived Inhibitors of the Proprotein Convertase Furin. ACS Med Chem Lett 2021, 12, 426-432.

Pászti-Gere, E., Pomothy, J., Jerzsele, Á., Pilgram, O., Steinmetzer, T. Exposure of human intestinal epithelial cells and primary human hepatocytes to trypsin-like serine protease inhibitors with potential antiviral effect. J Enzyme Inhib Med Chem 2021, 36, 659-668.

Schmitz, T., Paul George, A. A., Nubbemeyer, B., Bäuml, C. A., Steinmetzer, T., Ohlenschläger, O., Biswas, A., Imhof, D. NMR-Based Structural Characterization of a Two-Disulfide-Bonded Analogue of the FXIIIa Inhibitor Tridegin: New Insights into Structure-Activity Relationships. Int J Mol Sci 2021, 22, 880.

Sandner, A., Ngo, K., Schiebel, J., Pizarroso, A. I. M., Schmidt, L., Wenzel, B., Steinmetzer, T., Ostermann, A., Heine, A., Klebe, G. How a Fragment Draws Attention to Selectivity Discriminating Features between the Related Proteases Trypsin and Thrombin. J Med Chem 2021, 64, 1611-1625.

2020

Korff, M., Imberg, L., Will, J. M., Bückreiß, N., Kalinina, S. A., Wenzel, B. M., Kastner, G. A., Daniliuc, C. G., Barth, M., Ovsepyan, R. A., Butov, K. R., Humpf, H. U., Lehr, M., Panteleev, M. A., Poso, A., Karst, U., Steinmetzer, T., Bendas, G., Kalinin, D.V. Acylated 1H-1,2,4-Triazol-5-amines Targeting Human Coagulation Factor XIIa and Thrombin: Conventional and Microscale Synthesis, Anticoagulant Properties, and Mechanism of Action. J Med Chem 2020, 63, 13159-13186.

Hüttl, S., Hoffmann, M., Steinmetzer, T., Sauder, C., Krüger, N. The Amino Acid at Position 8 of the Proteolytic Cleavage Site of the Mumps Virus Fusion Protein Affects Viral Proteolysis and Fusogenicity. J Virol 2020, 94, e01732-20.

Bestle, D., Heindl, M. R., Limburg, H., Lam van, T. V., Pilgram, O., Moulton, H., Stein, D. A., Hardes, K., Eickmann, M., Dolnik, O., Rohde, C., Klenk, H. D., Garten, W., Steinmetzer, T., Böttcher-Friebertshäuser, E. TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells. Life science alliance 2020, 3, e202000786.

Bäuml, C. A., Paul George, A. A., Schmitz, T., Sommerfeld, P., Pietsch, M., Podsiadlowski, L., Steinmetzer, T., Biswas, A., Imhof, D. Distinct 3-disulfide-bonded isomers of tridegin differentially inhibit coagulation factor XIIIa: The influence of structural stability on bioactivity. Eur J Med Chem 2020, 201, 112474.

Braun, N. J., Quek, J. P., Huber, S., Kouretova, J., Rogge, D., Lang-Henkel, H., Cheong, E. Z.K., Chew, B. L. A., Heine, A., Luo, D., Steinmetzer, T. Structure-Based Macrocyclization of Substrate Analogue NS2B-NS3 Protease Inhibitors of Zika, West Nile and Dengue viruses. ChemMedChem 2020,15, 1439-1452.

Harbig, A., Mernberger, M., Bittel, L., Pleschka, S., Schughart, K., Steinmetzer, T., Stiewe, T., Nist, A., Böttcher-Friebertshäuser, E. Transcriptome profiling and protease inhibition experiments identify proteases that activate H3N2 influenza A and influenza B viruses in murine airways. J Biol Chem 2020, 295, 11388-11407.

Pászti-Gere, E., Szombath, G., Gütschow, M., Steinmetzer, T., Székács, A. 3-Amidinophenylalanine-derived matriptase inhibitors can modulate hepcidin production in vitro. Naunyn Schmiedebergs Arch Pharmacol 2020, 393, 511-520.

Steinmetzer, T., Pilgram, O., Wenzel, B.M., Wiedemeyer S. J. A. Fibrinolysis Inhibitors: Potential Drugs for the Treatment and Prevention of Bleeding. J Med Chem 2020, 63,1445-1472.

2019

Sandner, A., Hüfner-Wulsdorf, T., Heine, A., Steinmetzer, T., Klebe, G. Strategies for Late-Stage Optimization: Profiling Thermodynamics by Preorganization and Salt Bridge Shielding. J Med Chem 2019, 62, 9753-9771.

Lam van, T. V., Ivanova, T., Hardes, K., Heindl, M. R., Morty, R. E., Böttcher-Friebertshäuser, E., Lindberg, I., Than, M. E., Dahms, S. O., Steinmetzer, T. Design, Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin. ChemMedChem 2019, 14, 673-685.

Bäuml, C. A., Schmitz, T., Paul George, A. A., Sudarsanam, M., Hardes, K., Steinmetzer, T., Holle, L. A., Wolberg, A. S., Pötzsch, B., Oldenburg, J., Biswas, A., Imhof, D. Coagulation Factor XIIIa Inhibitor Tridegin: On the Role of Disulfide Bonds for Folding, Stability, and Function. J Med Chem 2019, 62, 3513-3523.

Löw, K., Hardes, K., Fedeli, C., Seidah, N. G., Constam, D. B., Pasquato, A., Steinmetzer, T., Roulin, A., Kunz, S. A novel cell-based sensor detecting the activity of individual basic proprotein convertases. FEBS J. 2019, 286, 4597-4620.

2018

Dahms, S. O., Hardes, K., Steinmetzer, T., Than, M. E. X-ray Structures of the Proprotein Convertase Furin Bound with Substrate Analogue Inhibitors Reveal Substrate Specificity Determinants beyond the S4 Pocket. Biochemistry 2018, 57, 925-934.

Phoo, W.W., Zhang, Z., Wirawan, M., Chew, E. J. C., Chew, A. B. L., Kouretova, J., Steinmetzer, T., Luo, D. Structures of Zika virus NS2B-NS3 protease in complex with peptidomimetic inhibitors. Antiviral Res. 2018, 160, 17-24.

Krüger, N., Sauder, C., Hüttl, S., Papies, J., Voigt, K., Herrler, G., Hardes, K., Steinmetzer, T., Örvell, C., Drexler, J.F., Drosten, C., Rubin, S., Müller, M. A., Hoffmann, M. Entry, Replication, Immune Evasion, and Neurotoxicity of Synthetically Engineered Bat-Borne Mumps Virus. Cell Rep. 2018, 25, 312-320.

Steinmetzer, T.; Hardes, K. The Antiviral Potential of Host Protease Inhibitors. In Activation of Viruses by Host Proteases. , Böttcher-Friebertshäuser E., Garten W., Klenk H. , Ed. Springer: 2018; pp 279-325.

2017

Voegeli R, Wikstroem P, Campiche R, Steinmetzer T, Jackson E, Gempeler M, Imfeld D, Rawlings AV The effects of benzylsulfonyl-D-Ser-homoPhe-(4-amidino-benzylamide), a dual plasmin and urokinase inhibitor, on facial skin barrier function in subjects with sensitive skin. Int J Cosmet Sci. 2017, 39, 109-120.

Jaegle M, Steinmetzer T, Rademann J. Protein-Templated Formation of an Inhibitor of the Blood Coagulation Factor Xa through a Background-Free Amidation Reaction. Angew Chem Int Ed Engl. 2017 Mar 20;56(13):3718-3722.

Hardes K, Ivanova T, Thaa B, McInerney GM, Klokk TI, Sandvig K, Künzel S, Lindberg I, Steinmetzer T. Elongated and shortened peptidomimetic inhibitors of the proprotein convertase furin. ChemMedChem. 2017, 12, 613-620

Häussler, D.; Schulz-Fincke, A. C.; Beckmann, A. M.; Keils, A.; Gilberg, E.; Mangold, M.; Bajorath, J.; Stirnberg, M.; Steinmetzer, T.; Gütschow, M. A Fluorescent-Labeled Phosphono Bisbenzguanidine As an Activity-Based Probe for Matriptase. Chemistry 2017, 23, 5205-5209.

Kouretova, J.; Hammamy, M. Z.; Epp, A.; Hardes, K.; Kallis, S.; Zhang, L.; Hilgenfeld, R.; Bartenschlager, R.; Steinmetzer, T. Effects of NS2B-NS3 protease and furin inhibition on West Nile and Dengue virus replication. J Enzyme Inhib Med Chem 2017, 32, 712-721.

Wilkinson, D. J.; Habgood, A.; Lamb, H. K.; Thompson, P.; Hawkins, A. R.; Desilets, A.; Leduc, R.; Steinmetzer, T.; Hammami, M.; Lee, M. S.; Craik, C. S.; Watson, S.; Lin, H.; Milner, J. M.; Rowan, A. D. Matriptase Induction of Metalloproteinase-Dependent Aggrecanolysis In Vitro and In Vivo: Promotion of Osteoarthritic Cartilage Damage by Multiple Mechanisms. Arthritis & Rheumatology 2017, 69, 1601-1611.

Ivanova, T.; Hardes, K.; Kallis, S.; Dahms, S. O.; Than, M. E.; Künzel, S.; Böttcher-Friebertshäuser, E.; Lindberg, I.; Jiao, G. S.; Bartenschlager, R.; Steinmetzer, T. Optimization of Substrate-Analogue Furin Inhibitors. ChemMedChem 2017, 12, 1953-1968.

2016

Paszti-Gere, E.; Barna, R. F.; Ujhelyi, G.; Steinmetzer, T. Interaction exists between matriptase inhibitors and intestinal epithelial cells. J Enzyme Inhib Med Chem 2016, 31, 736-741.

Lennartz, F.; Bayer, K.; Czerwonka, N.; Lu, Y.; Kehr, K.; Hirz, M.; Steinmetzer, T.; Garten, W.; Herden, C. Surface glycoprotein of Borna Disease virus mediates virus spread from cell to cell. Cell Microbiol 2016, 18, 340-354.

Furtmann, N., Häußler, D., Scheidt, T., Stirnberg, M., Steinmetzer, T., Bajorath, J., Gütschow, M. Limiting the Number of Potential Binding Modes by Introducing Symmetry into Ligands: Structure-Based Design of Inhibitors for Trypsin-Like Serine Proteases. Chem Eur . 2016, 22, 610 –625.

Endreas, W., Brüßler, J., Vornicescu, D., Keusgen, M., Bakowsky, U., Steinmetzer T.  Thrombin-inhibiting anticoagulant liposomes – development and characterization. ChemMedChem 2016, 11, 340-349.

Coburger, I., Schaub, Y., Roeser, D., Hardes, K., Maeder, P., Klee, N., Steinmetzer, T., Imhof, D., Diederich, W. E., Than, M. E. Identification of inhibitors of the transmembrane protease FlaK of Methanococcus maripaludis. MicrobiologyOpen, 2016, 5, 637-646.

Maiwald A, Hammami M, Wagner S, Heine A, Klebe G, Steinmetzer T. Changing the selectivity profile - from substrate analog inhibitors of thrombin and factor Xa to potent matriptase inhibitors. J. Enzyme Inhib Med Chem 2016, 31 (S1), 89-97.

Pászti-Gere E, Czimmermann E, Ujhelyi G, Balla P, Maiwald A, Steinmetzer T. In vitro characterization of TMPRSS2 inhibition in IPEC-J2 cells. J Enzyme Inhib Med Chem. 2016, 31(S2), 123-129.

Hinkes S, Wuttke A, Saupe SM, Ivanova T, Wagner S, Knörlein A, Heine A, Klebe G, Steinmetzer T. Optimization of Cyclic Plasmin Inhibitors: From Benzamidines to Benzylamines. J Med Chem. 2016, 59, 6370-6386.

Pomothy J, Szombath G, Rokonál P, Mátis G, Neogrády Z, Steinmetzer T, Pászti-Gere E. The Impact of Acute Matriptase Inhibition in Hepatic Inflammatory Models. Biomed Res Int. 2016, 2016, 6306984.

Dahms SO, Arciniega M, Steinmetzer T, Huber R, Than ME. Structure of the unliganded form of the proprotein convertase furin suggests activation by a substrate-induced mechanism. Proc Natl Acad Sci U S A. 2016, 113, 11196-11201.

Braun F, Bertoletti N, Möller G, Adamski J, Steinmetzer T, Salah M, Abdelsamie AS, van Koppen CJ, Heine A, Klebe G, Marchais-Oberwinkler S. First Structure-Activity Relationship of 17β-Hydroxysteroid Dehydrogenase Type 14 Nonsteroidal Inhibitors and Crystal Structures in Complex with the Enzyme. J Med Chem. 2016, 59, 10719-10737.

2015

Hardes, K.; Becker, G. L.; Lu, Y.; Dahms, S. O.; Köhler, S.; Beyer, W.; Sandvig, K.; Yamamoto, H.; Lindberg, I.; Walz, L.; von Messling, V.; Than, M. E.; Garten, W.; Steinmetzer, T. Novel Furin Inhibitors with Potent Anti-infectious Activity. ChemMedChem 2015, 10, 1218-31.

Lu, Y.; Hardes, K.; Dahms, S. O.; Böttcher-Friebertshäuser, E.; Steinmetzer, T.; Than, M. E.; Klenk, H. D.; Garten, W. Peptidomimetic furin inhibitor MI-701 in combination with oseltamivir and ribavirin efficiently blocks propagation of highly pathogenic avian influenza viruses and delays high level oseltamivir resistance in MDCK cells. Antiviral Res 2015, 120, 89-100.

Garten, W.; Braden, C.; Arendt, A.; Peitsch, C.; Baron, J.; Lu, Y.; Pawletko, K.; Hardes, K.; Steinmetzer, T.; Böttcher-Friebertshäuser, E. Influenza virus activating host proteases: Identification, localization and inhibitors as potential therapeutics. Eur J Cell Biol 2015, 94, 375-83.

Steinmetzer, T.; Hardes, K.; Böttcher-Friebertshäuser, E.; Garten, W. Strategies for the Development of Influenza Drugs: Basis for New Efficient Combination Therapies. In Therapy of Viral Infections, Diederich, W. E.; Steuber, H., Eds. Springer Berlin Heidelberg: 2015; Vol. 15, pp 143-181.

Paszti-Gere, E.; Barna, R. F.; Ujhelyi, G.; Steinmetzer, T. Interaction exists between matriptase inhibitors and intestinal epithelial cells. J Enzyme Inhib Med Chem 2015, 31:5, 736-741. https://doi.org/10.3109/14756366.2015.1060483

Häussler, D.; Scheidt, T.; Stirnberg, M.; Steinmetzer, T.; Gütschow, M. A Bisbenzamidine Phosphonate as a Janus-faced Inhibitor for Trypsin-like Serine Proteases. ChemMedChem 2015, 10, 1641-1646.

Lennartz, F.; Bayer, K.; Czerwonka, N.; Lu, Y.; Kehr, K.; Hirz, M.; Steinmetzer, T.; Garten, W.; Herden, C. Surface glycoprotein of Borna Disease virus mediates virus spread from cell to cell. Cell Microbiol 2015, 18, 340-354 https://doi.org/10.1111/cmi.12515

Pászti-Gere, E., McManus, S., Meggyesházi, N., Balla, P., Gálfi, P., Steinmetzer T. Inhibition of Matriptase Activity Results in Decreased Intestinal Epithelial Monolayer Integrity In Vitro. PLoS One 2015 Oct 21;10(10):e0141077.

2014

Dahms, S. O.; Hardes, K.; Becker, G. L.; Steinmetzer, T.; Brandstetter, H.; Than, M. E. X-ray structures of human furin in complex with competitive inhibitors. ACS Chem Biol 2014, 9, 1113-8.

Grüner, S.; Neeb, M.; Barandun, L. J.; Sielaff, F.; Hohn, C.; Kojima, S.; Steinmetzer, T.; Diederich, F.; Klebe, G. Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics. Biochim Biophys Acta 2014, 1840, 2843-50.

Tziridis, A.; Rauh, D.; Neumann, P.; Kolenko, P.; Menzel, A.; Bräuer, U.; Ursel, C.; Steinmetzer, P.; Stürzebecher, J.; Schweinitz, A.; Steinmetzer, T.; Stubbs, M. T. Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues. Biol Chem 2014, 395, 891-903.

Böhm, M.; Bäuml, C. A.; Hardes, K.; Steinmetzer, T.; Roeser, D.; Schaub, Y.; Than, M. E.; Biswas, A.; Imhof, D. Novel insights into structure and function of factor XIIIa-inhibitor tridegin. J Med Chem 2014, 57, 10355-65.

2013

Baron. J., Tarnow, C., Mayoli-Nüssle, D., Schilling, E., Meyer, D., Hammami, M., Schwalm, F., Steinmetzer, T., Guan, Y., Garten, W., Klenk, H.D., Böttcher-Friebertshäuser E. (2013) Matriptase, HAT and TMPRSS2 activate the hemagglutinin of H9N2 influenza A viruses. J. Virol. 87, 1811-1820.

Hammamy, M.Z., Haase, C., Hammami, M., Hilgenfeld, R., Steinmetzer, T. (2013) Development and characterization of new peptidomimetic inhibitors of the West Nile virus NS2B-NS3 protease. ChemMedChem 8, 231–241.

Saupe, S.M., Leubner, S., Betz, M., Klebe, G., Steinmetzer, T. (2013) Development of new cyclic plasmin inhibitors with excellent potency and selectivity. J. Med. Chem. 56, 820–831.

Meyer, D., Sielaff, F., Hammami, M., Böttcher-Friebertshäuser, E., Garten, W., Steinmetzer, T. (2013) Identification of the first synthetic inhibitors of the type II transmembrane serine protease TMPRSS2 suitable for inhibition of influenza virus activation. Biochem J. 425, 331-343.

Hardes, K., Hammamy, M. Z., Steinmetzer, T. (2013) Synthesis and characterization of novel fluorogenic substrates of coagulation factor XIII-A. Anal. Biochem. 442, 223-230.

2012

Böhm, M., Kühl, T., Hardes, K., Coch, R., Arkona, C., Schlott, B., Steinmetzer, T., Imhof D. (2012) Synthesis and functional characterization of tridegin and its analogues: Inhibitors and substrates of factor XIIIa. ChemMedChem 7, 326-333.

Saupe, S.M., Steinmetzer T. (2012) A New Strategy for the Development of Highly Potent and Selective Plasmin Inhibitors.  J. Med. Chem.  55, 1171-1180.

Becker, G.L., Lu, Y., Hardes, K., Strehlow, B., Levesque, C., Lindberg, I., Sandvig, K., Bakowsky, U., Day, R., Garten, W., Steinmetzer, T. (2012) Highly potent inhibitors of the proprotein convertase furin as potential drugs for the treatment of infectious diseases. J. Biol. Chem. 287, 21992-22003.

Biela, A., Sielaff, F., Terwesten, F., Heine, A., Steinmetzer, T., Klebe, G. (2012) Ligand binding gradually disrupts water network in thrombin: Enthalpic and entropic changes reveal classical hydrophobic effect. J. Med. Chem. 55, 6094-6110.

Hardes, K., Becker, G.L., Hammamy M.Z., Steinmetzer, T. (2012) Design, synthesis and characterization of chromogenic substrates of coagulation factor XIIIa. Anal. Biochem. 428, 73-80.

Hammami M., Rühmann, E., Maurer, E., Heine, A., Gütschow, M., Klebe, G., Steinmetzer, T. (2012) New 3-amidinophenylalanine derived inhibitors of matriptase. MedChemComm 3, 807-813.

Böttcher-Friebertshäuser, E., Lu, Y., Meyer, D., Sielaff, F., Steinmetzer, T., Klenk, H.-D.,Garten, W. (2012) Hemagglutinin activating host cell proteases provide promising drug targets for the treatment of influenza A and B virus infections. Vaccine 30, 7374-7380 

Cubrilovic, D., Biela, A., Sielaff, F., Steinmetzer, T., Klebe, G., Zenobi, R. (2012) Quantifying Protein-Ligand Binding Constants using Electrospray Ionization Mass Spectrometry: A Systematic Binding Affinity Study of a Series of Hydrophobically Modified Trypsin Inhibitors. J Am Soc Mass Spectrom 23, 1768-1777

Steinmetzer, T., Baum, B., Biela, A., Klebe, G., Nowak, G., Bucha, E. (2012) Beyond Heparinization: Design of highly potent thrombin inhibitors suitable for surface coupling. ChemMedChem 7, 1965-1973. 

2011

Sielaff, F., Than, M.E., Bevec, D., Lindberg, I., Steinmetzer, T. (2011) New furin inhibitors based on weakly basic amidinohydrazones. Bioorg. Med. Chem. Lett. 21, 836-840.

Kotthaus, J., Steinmetzer, T., van de Locht, A., Clement, B. (2011) Analysis of highly potent amidine containing inhibitors of serine proteases and their N-hydroxylated prodrugs (amidoximes). J. Enz. Inhib. Med. Chem.26, 115-122.

Steinmetzer, T. (2011) Strategien für die Entwicklung neuartiger Grippemittel. Pharmazie in unserer Zeit 40, 160-168.

Sielaff, F., Böttcher-Friebertshäuser, E., Meyer, D., Saupe, S.M., Volk, I.M., Garten, W.,  Steinmetzer, T. (2011) Development of substrate analogue inhibitors for the human airway trypsin-like protease HAT. Bioorg. Med. Chem. Lett. 21, 4860-4864.

Becker, G.L., Hardes, K., Steinmetzer, T. (2011) New substrate analogue furin inhibitors derived from 4-amidinobenzylamide. Bioorg. Med. Chem. Lett. 21, 4695-4697.

Kuester, M., Becker, G.L., Hardes, K., Lindberg, I., Steinmetzer, T., Than, M.E. (2011) Purification of the proprotein convertase furin by affinity chromatography based on PC-specific inhibitors. Biol. Chem. 392, 973-981.

2010

Becker, G.L., Sielaff, F., Than, M.E., Lindberg, I., Routhier, S., Day, R., Lu, Y., Garten, W., Steinmetzer, T. (2010) Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics. J. Med. Chem. 53, 1067-1075.

Kotthaus J, Steinmetzer T, Kotthaus J, Schade D, van de Locht A, Clement B. (2010) Metabolism and distribution of two highly potent and selective peptidomimetic inhibitors of matriptase. Xenobiotica 40, 93-101.

Böttcher-Friebertshäuser E, Freuer C, Sielaff F, Schmidt S, Eickmann M, Uhlendorff J, Steinmetzer T, Klenk HD, Garten W. (2010) Cleavage of influenza virus hemagglutinin by airway proteases TMPRSS2 and HAT differs in subcellular localization and susceptibility to protease inhibitors. J. Virol. 84, 5605-5614.

Napp, J., Dullin, C., Müller, F., Uhland, K., Petri, J.P., van de Locht, A., Steinmetzer, T., Alves, F. (2010) Time-domain in vivo near infrared fluorescence imaging for evaluation of matriptase as a potential target for the development of novel, inhibitor-based tumour therapies. Int. J. of Cancer 127, 1958-1974.

Sisay, M.T., Steinmetzer, T., Stirnberg, M., Maurer, E., Hammami, M., Bajorath, J., Gütschow, M. (2010) Identification of the first low-molecular-weight inhibitors of matriptase-2. J. Med. Chem. 53, 5523-5535.

2009

Böttcher, E., Freuer, C., Steinmetzer, T., Klenk, H.-D., Garten, W. (2009) MDCK cells expressing proteases TMPRSS2 and HAT provide a cell system to propagate influenza viruses in the absence of trypsin and to study clevage of HA and its inhibition. Vaccine 27, 6324-6329.

Uhland, K., Siphos, B., Arkona, C., Schuster, M., Petri, B., Steinmetzer, P., Mueller, F., Schweinitz, A., Steinmetzer, T., van de Locht, A. (2009) Use of IHC and newly designed matriptase inhibitors to elucidate the role of matriptase in pancreatic ductal adenocarcinoma. Int. J. Oncology 35, 347-357.

Schweinitz, A., Dönnecke, D., Ludwig, A., Steinmetzer, P., Schulze, A., Kotthaus, J., Wein, S., Clement, B., Steinmetzer, T. (2009) Incorporation of neutral C-terminal residues in matriptase inhibitors derived from sulfonylated secondary amides of 3-amidinophenylalanine. Bioorg. Med. Chem. Lett. 19, 1960-1965.

Steinmetzer, T., Dönnecke, D., Korsonewski, M., Neuwirth, C., Steinmetzer, P., Schulze, A., Saupe, S.M., Schweinitz, A. (2009) Modification of the N-terminal sulfonyl residue in 3-amidinophenylalanine-based matriptase inhibitors. Bioorg. Med. Chem. Lett. 19, 67-73.

2008

Steinmetzer, T., Schweinitz, A., Stürzebecher, J., Steinmetzer, P., Söffing, A., van de Locht, A., Nicklisch, S., Reichelt, C., Ludwig, F.-A., Schulze, A., Daghisch, M., Heinicke, J. (2008) Trypsinartige Serinproteasehemmstoffe, ihre Herstellung und Verwendung. WO2008/049595.

Steinmetzer, T., Schweinitz, A., Dönnecke, D. (2008) Meta-substituierte Phenylsulfonylamide sekundärer Aminosäureamide als Hemmstoffe der Matriptase zur Hemmung des Tumorwachstums und/oder der Metastasierung von Tumoren. WO 2008/107176.

2007

Dönnecke, D., Schweinitz, A., Stürzebecher, A., Steinmetzer, P., Schuster, M., Stürzebecher, U., Nicklisch, S., Stürzebecher, J., Steinmetzer, T. (2007) From selective substrate analogue factor Xa inhibitors to dual inhibitors of thrombin and factor Xa: Part 3. Bioorg. Med. Chem. Lett. 17, 3322-3329.

Stürzebecher, A., Dönnecke, D., Schweinitz, A., Schuster, O., Steinmetzer, P., Stürzebecher, U., Stürzebecher, Kotthaus, J., Clement, B., Steinmetzer, T. (2007) Highly potent and selective substrate analogue factor Xa inhibitors containing d homophenylalanine analogues as P3 residue: Part 2. ChemMedChem 2, 1043-1053.

Steinmetzer, T., Dönnecke, D., Schweinitz, A., Stürzebecher, A., Stürzebecher, J. (2007) 2-(Aminomethyl)-5-Chlor-Benzylamid-Derivate und ihre Verwendung als Hemmstoffe des Gerinnungsfaktors Xa. WO 2007/031343.

2006

Steinmetzer, T., Schweinitz, A., Stürzebecher, A., Dönnecke, D., Uhland, K., Schuster, O., Müller, F., Friedrich, R., Than, M.E., Bode, W., Stürzebecher, J. (2006) New sulfonylated derivatives of 3-amidinophenylalanine as potent and selective matriptase inhibitors. J. Med. Chem. 49, 4116-4126.

Schweinitz, A., Stürzebecher, A., Stürzebecher, U., Schuster, O., Stürzebecher, J., Steinmetzer, T. (2006) New substrate analogue inhibitors of factor Xa containing 4-amidinobenzylamide as P1 residue: Part 1. Medicinal Chemistry 2, 349-361.

2005

Förbs, D., Thiel, S., Stella, M. C., Stürzebecher, A., Schweinitz, A., Steinmetzer, T., Stürzebecher, J., Uhland, K. (2005) In vitro inhibition of matriptase prevents invasive growth through HGF/SF-dependent and HGF/SF-independent pathways. Int. Journal of Oncology 27, 1061-1070.

Steinmetzer, T. (2005) Thrombin inhibitor examples. In: Enzymes and their inhibition: Drug development. ed. by Smith, H.J. and Simons, C., CRC Press, Boca Raton, London, New York, Washington D.C., pp. 254-268.

Patel, A., Smith, H.J., Steinmetzer, T. (2005) Design of enzyme inhibitors as drugs. In: Introduction to the principles of drug design and action. ed. by Smith, H.J., Taylor & Francis, 4. Auflage. chapter 9, pp. 257-326.

Stürzebecher, J., Steinmetzer, T., Schweinitz, A., Stürzebecher, A. (2005) Basisch-substituierte Benzylaminanaloga als Inhibitoren des Gerinnungsfaktors Xa, ihre Herstellung und Verwendung. WO 2005/026198.

2004

Steinmetzer, T., Stürzebecher, J. (2004) Progress in the development of synthetic thrombin inhibitors as new orally active anticoagulants. Current Medicinal Chemistry 11, 2297-2321.

Steinmetzer, T., Stürzebecher, J. (2004) Von Fibrinogen und Hirudin zu synthetischen Antikoagulanzien - rationales Design von Thrombinhemmstoffen. Pharmazie in unserer Zeit 33, 196-205.

Schweinitz, A., Steinmetzer, T., Banke, I.J., Arlt, M.J.E., Stürzebecher, A., Schuster, O., Geissler, A., Giersiefen, H., Zeslawska, E., Jacob, U., Krüger, A., Stürzebecher, J. (2004) Design of novel and selective inhibitors of the urokinase-type plasminogen activator with improved pharmacokinetic properties for the use as antimetastatic agents. J. Biol. Chem. 279, 33613-33622.

Stürzebecher, J., Steinmetzer, T., Schweinitz, A. (2004) Verwendung von acylierten 4-Amidino- und 4-Guanidinobenzylaminen zur Inhibierung von Plasmakallikrein. WO 2004/062657.

Stürzebecher, J., Steinmetzer, T., Schweinitz, A., Stürzebecher, A. (2004) N-Sulfonylierte Aminosäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung. WO 2004/101507.

2003

Steinmetzer, T. (2003) Synthetic urokinase inhibitors as potential antitumor drugs. IDrugs 6, 138-146.

Banke, I.J., Arlt, M.J.E., Pennington, C., Kopitz, C., Steinmetzer, T., Schweinitz, A., Gansbacher, B., Quigley, J.P., Edwards, D.R., Stürzebecher, J., Krüger, A. (2003) Increase of anti-metastatic efficacy by selectivity- but not affinity-optimization of synthetic serine protease inhibitors. Biological Chemistry 384, 1515-1525.

López, M., Mende, K., Steinmetzer, T., Nowak, G. (2003) Cloning, purification and biochemical characterization of dipetarudin, a new chimeric thrombin inhibitor. J. Chromatography B 786, 73-80.

Stürzebecher, J., Steinmetzer, T., Schweinitz, A. (2003) Hemmstoffe der Urokinase, ihre Herstellung und Verwendung. WO 2003/076391.

Stürzebecher, J., Steinmetzer, T., Schweinitz, A. (2003) Hemmstoffe des Gerinnungsfaktors Xa, ihre Herstellung und Verwendung. WO 2003/076457.

2002

Hauptmann, J., Steinmetzer, T., Vieweg, H., Wikström, P., Stürzebecher, J. (2002) Influence of structural variations in peptidomimetic 4-amidinophenylalanine-derived thrombin inhibitors on plasma clearance an biliary excretion in rats. Pharmaceutical Res. 19, 1027-1033.

Friedrich, R., Steinmetzer, T., Huber, R., Stürzebecher, J., Bode, W. (2002) The methyl group of Nα(Me)Arg-containing peptides disturbs the active-site geometry of thrombin, impairing efficient cleavage. J. Mol. Biol. 316, 869-874.

Künzel, S., Schweinitz, A., Reissmann, S., Stürzebecher, J., Steinmetzer, T. (2002) 4-Amidinobenzylamine-based inhibitors of urokinase. Bioorganic Medicinal Chemistry Lett. 12, 645-648.

Stürzebecher, J., Hauptmann, J., Steinmetzer, T. (2002) Thrombin. In: Proteinase and Peptidase Inhibition: Recent Potential Targets for Drug Development, ed. by Smith, H.J. and Simons, C., Taylor & Francis, London, New York, pp. 178-201.

Reissmann, S., Steinmetzer, T., Greiner, G., Seyfarth, L., Besser, D., Schumann, C. (2002) Hydroxy group. In: Houben-Weyl, Volume E22a 'Synthesis of Peptides and Peptidomimetics', ed. by Goodman, M., Felix, A., Moroder, L., Toniolo, C., Georg Thieme Verlag, Stuttgart and New York, pp. 347-378.

Steinmetzer, T., Nowak, G. (2002) Oligo- oder Polyalkylenglycol-gekoppelte Thrombininhibitoren. WO 02/059065.

2001

Steinmetzer, T., Hauptmann, J., Stürzebecher, J. (2001) Advances in the development of thrombin inhibitors. Exp. Opin. Invest. Drugs 10, 845-864.

Steinmetzer, T., Schweinitz, A., Künzel, S., Wikström, P., Hauptmann, J., Stürzebecher, J. (2001) Structure-activity relationships of new NAPAP-analogs. J. Enzyme Inhibition 16, 241-249.

Stürzebecher, J., Steinmetzer, T., Künzel, S., Schweinitz, A. (2001) Urokinase-Hemmstoffe. WO 01/96286.

Stürzebecher, J., Steinmetzer, T., Künzel, S., Schweinitz, A. (2001) Hemmstoffe für den Gerinnungsfaktor Xa. WO 01/96366.

2000

Besser, D., Müller, B., Kleinwächter, P., Greiner, G., Seyfarth, L., Steinmetzer, T., Arad, O., Reissmann, S. (2000) Synthesis and Characterization of octapeptide somatostatin analoques with backbone cyclization: Comparison of different strategies, biological activities and enzymatic stabilities. J. Prakt. Chem. 342, 537-545.

Predel, R., Kellner, R., Baggerman, G., Steinmetzer, T., Schoofs, L. (2000) Identification of novel periviscerokinins from single neurohaemal release sites in insects. MS/MS fragmentation completed by Edman degradation. European J. Biochem. 267, 3869-3873.

Steinmetzer, T., Batdordshjin, M., Pineda, F., Seyfarth, L., Vogel, A., Reißmann, S., Hauptmann, J., Stürzebecher, J. (2000) New bivalent thrombin inhibitors with N^(Methyl)Arginine at the P1-Position. Biol. Chem. 381, 603-610.

Pineda, L.F., Liebmann, C., Henselek, S., Paegelow, I., Steinmetzer, T., Schweinitz, Stürzebecher, J., A., Reißmann, S. (2000) Novel non-peptide lead structures for bradykinin B2-receptor antagonists. Lett. in Pept. Science 7, 69-77.

1999

Stürzebecher, J., Vieweg, H., Steinmetzer, T., Schweinitz, A., Stubbs, M.T., Renatus, M., Wikström, P. (1999) 3-Amidinophenylalanine-based Inhibitors of Urokinase. Bioorganic & Medicinal Chemistry Letters 9, 3147-3152.

Hoffmann, D., Kramer, B., Washio, T., Steinmetzer, T.Rarey, M., Lengauer, T. (1999) A two-stage method for protein-ligand docking. J. Med. Chem. 42, 4422-4433.

Steinmetzer, T., Renatus, M., Künzel, S., Eichinger, A., Wikström, P., Hauptmann, J., Stürzebecher, J. (1999) Design and evaluation of novel bivalent thrombin inhibitors based on amidinophenylalanines. European J. Biochemistry 265, 598-605.

Steinmetzer, T., Zhu, B.Y., Konishi, Y. (1999) Potent Bivalent Thrombin Inhibitors: Replacement of the Scissile Peptide Bond at P1-P1' with Arginyl Ketomethylene Isosteres. J. Med. Chem., 42, 3109-3115.

Steinmetzer, T., Batdorsdhjin, M., Kleinwächter, P., Seyfarth, L., Greiner, G., Reißmann, S., Stürzebecher, J. (1999) New thrombin inhibitors based on D-Cha-Pro-derivatives. J. Enzyme Inhibition 14, 203-216.

1996

Liebmann, C., Graneß, A., Boehmer, A., Kovalenko, M., Adomeit, A., Steinmetzer, T., Nürnberg, B., Wetzker, R., Boehmer, F.D. (1996) Tyrosine Phophorylation of Gs and Inhibition of Bradykinin-Induced Activation of the cyclic AMP Pathway in A431 Cells by Epidermal Growth Factor Receptor. J. Biol. Chem. 271, 31098-31105.

Steinmetzer, T., Konishi, Y. (1996) Tripeptidyl pyridinium methyl ketones as potent active site inhibitors of thrombin. Bioorganic & Medicinal Chemistry Letters 6, 1677-1682.

1995

Rehse, P.H., Steinmetzer, T., Li, Y., Konishi, Y., Cygler, M. (1995) Crystal structure of a peptidyl pyridinium methyl ketone inhibitor with thrombin. Biochemistry 34, 11537 - 11544.

Schumann, C., Steinmetzer, T., Gothe, R., Hoppe, A., Paegelow, I., Liebmann, C., Fabry, M., Brandenburg, D., Reißmann, S. (1995) Potent photoaffinity labelled and iodinated antagonists of bradykinin. Biol. Chem. Hoppe-Seyler 376, 33 - 38.

Steinmetzer, T., Schumann, C., Paegelow, I., Liebmann, C., Glasmacher, D., Brandenburg, D., Reißmann, S. (1995) New photoaffinity labelled agonists of bradykinin. Biol. Chem. Hoppe-Seyler 376, 25 - 32.

DiMaio, J., Konishi, Y., Ni, F., Steinmetzer, T. (1995) Thrombin inhibitors based on the amino acid sequence of hirudin US6,060,451.

1993

Steinmetzer, T., Silberringt, J., Mrestani-Klaus, C., Fittkau, S., Barth, A., Demuth, H.-U. (1993) Peptidyl ammonium methyl ketones as substrate analog inhibitors of proline-specific peptidases. J. Enzyme Inhibition 7, 77-85.

1991

Schön, E., Born, I., Demuth, H.-U., Faust, J., Neubert, K., Steinmetzer, T., Barth, A., Ansorge, S. (1991) Dipeptidyl peptidase IV in the immune system: Effects of specific enzyme inhibitors on activity of dipeptidyl peptidase IV and proliferation of human lymphocytes. Biol. Chem. Hoppe-Seyler 372, 305 - 311.

Neumann, U., Steinmetzer, T., Barth, A., Demuth, H.-U. (1991) Reaction of dipeptidyl peptidase IV with substrate-analogous azapeptides. J. Enzyme Inhibition 4, 213 - 226.

1990

Barth, A., Demuth, H. U., Fittkau, S., Steinmetzer, T. (1990) Neue Inhibitoren zur Hemmung der katalytischen Aktivität von prolinspezifischen und anderen proteolytischen Enzymen und Verfahren zu ihrer Herstellung. DD 294 176.

1989

Neubert, C., Born, I., Faust, J., Heins J., Barth, A., Demuth, H.-U., Rahfeld, J. U., Steinmetzer, T. (1989) Verfahren zur Herstellung neuer Inhibitoren der Dipeptidyl Pepetidase IV. DD 296 075.

1988

Lasch, J., Koelsch, R., Steinmetzer, T., Neumann, U., Demuth, H.-U. (1988) Enzymic properties of intestinal aminopeptidase P: a new continous assay. FEBS Letters 227, 171-174.