Entwicklung von synthetischen Inhibitoren für Matrixmetalloproteinasen (MMPs) und ADAMs

• Applicant: Professor Dr. Harald Tschesche
• Subject Area: Biochemistry
• Term: from 1998 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5083288

• Final Report Year: 2008

Final Report Abstract

No abstract available

Publications

• Hydroxamate derivatives of substrate-analogous peptides containing aminomalonic acid are potent inhibitors of matrix metalloproteinases. FEBS Lett. 436, 209-212 (1998)
  D. Krumme, H. Wenzel & H. Tschesche
  
• Synthesis and reduction of endothiodipeptides containing malonic acid derivatives. Tetrahedon 55, 3007-3018 (1999)
  D. Krumme & H. Tschesche
  
• Protease Inhibitors. In: Protein Engineering by Semi synthesis (C.A.Wallace, ed.) CRC Press Boca Raton, 209-231 (2000)
  H.R. Wenzel & H.Tschesche
  
• Timp-2 acts synergistically with synthetic MMP inhibitors but not with TIMP-4 to enhance the MT1-MMP-dependent activation of Pro-MMP-2. J. Biol. Chem. 275, 41415-41423 (2000)
  M. Toth, M.M. Bernardo, D.C. Gervasi, P.D. Soloway, Z. Wang, H.F. Bigg, C.M. Overall, Y.A. DeClerk, H. Tschesche, M.L. Cher, S. Brown, S.Mobashery & F. Fridman
  
• Two crystal structures of human neutrophil collagenase, one complexed with a primed and the other with an unprimed-side inhibitor: Implications for drug design. J. Med. Chem. 43, 3377 - 3385 (2000)
  E. Gavuzzo, G. Pochetti, F. Mazza, C. Gallina, B. Gorini, S. D'Alessio, M. Pieper, H. Tschesche & P.A. Tucker
  
• Novel heterocyclic inhibitors of matrix metalloproteinases: Three 6H-1,3,4- Thiadiazines. Acta Cryst. C57, 593-596 (2001)
  J.Schröder, H.Wenzel, H.G.Stammler, A.Stammler, B.Neumann & H.Tschesche
  
• Structure-based Design and Synthesis of Potent Matrix Metalloproteinase Inhibitors Derived from a 6H-12,3,4-Thiadiazine Scaffold. J. Med. Chem. 44, 3231-3243 (2001)
  J. Schröder, A.Henke, H. Wenzel, H.Brandstetter, H.G.Stammler, W.D.Pfeiffer & H. Tschesche
  
• Substrate Specificity Determinants of Human Macrophage Elastase (MMP-12) Based on the 1.1 Angstrom Crystal Structure. J.Mol.Biol. 312(4), 731-742 (2001)
  R.Lang, A.Kocourek, M.Braun, H.Tschesche, R.Huber, W.Bode & Kl.Maskos
  
• 3D Structure and Drug Design. In: Proteases and their Inhibitors in Cancer Metastasis, J.M.Foidart & RJ.Muschel, Hrsgb., Klüwer Acad. Publ., Dordrecht, Boston, London, p. 127-150 (2002)
  J.Schröder, H. Wenzel & H. Tschesche
  
• Computational study of the catalytic domain of human neutrophil collagenase. Specific role of the S3 and S31 subsites in the interaction with a phosphonate inhibitor. J. Comput.-Aided Molec. Design 16, 213-225 (2002)
  M.Aschi, D.Roccatano, A. Di Nola, C.Gallina, E.Gavuzzo, G.Pochetti, M.Pieper, H.Tschesche & F. Mazza
  
• Oxal Hydroxamic Acid Derivatives with Inhibitory Activity against Matrix Metalloproteinases. Bioorganic & Medicinal Chem. Letters 12, 933-936 (2002)
  D.Krumme & H. Tschesche
  
• Catalytic- and ecto-domains of membrane type 1-matrix metalloproteinase have similar inhibition profiles but distinct endopeptidase activities. Biochem. J. 377, 775 - 779 (2004)
  D.R. Hurst, M.A. Schwartz, M.A. Ghaffari, Y.H. Jin, H. Tschesche, G.B. Fields & QXA.Sang
  
• Structural Insight into the stereoselective Inhibition of MMP-8 by Enantiomeric Sulfonamide Phosphonates. J. Med. Chem. 49, 923 - 931 (2006)
  G. Pochetti, E. Gavuzzo, C. Campestre, M. Agamennone, P. Tortorella, V. Consalvi, C. Gallina, O. Hiller, H. Tschesche, P.A. Tucker & F. Mazza
  
• Characterisation of a Novel Matrix Metalloproteinase-Inhibitor on Pancreatic Adenocarcinoma Cells in vitro and in an Orthotopic Pancreatic Cancer Model in vivo. Intern. J. Oncology 32, 273-282 (2008)
  M. Kapischke, T. Fischer, K. Tiessen, J. Tepel, H. Tschesche, H.-P. Bruch, H. Kalthoff & M.-L. Kruse