Selective integrin inhibitors for application as drugs, for coating biomaterials and for molecular imaging
Event details
| Date | 06.11.2013 |
| Hour | 17:15 › 18:30 |
| Speaker | Prof. Dr. Horst Kessler, Institute for Advanced Study, Technische Universität München, Garching Technische Universität München (TUM), Department Chemistry, Garching/Munich, Germany |
| Location | |
| Category | Conferences - Seminars |
Cell adhesion is mediated via cellular bidirectional receptors, so-called integrins. The tripeptidic sequence RGD is recognized by several integrin subtypes (v3, v5, v6, v8, 51, IIb3). The different integrins recognize different extracellular matrix proteins and the integrin pattern on cells strongly depend on many factors. Superactivity and receptor subtype selectivity has been achieved by the “spatial screening” procedure which yielded the cyclic peptides c(RGDfX) as the first selective and superactive ligand for αvβ3. This lead structure was optimized by development of peptidomimetics to achieve subtype selectivity, especially between the integrins αvβ3 and α5β1. Different functionalization under retention of their activity and selectivity profiles allow biophysical studies regarding the function of different integrin subtypes and coating of implant materials to stimulate osteoblast adhesion in bone implants or to prevent restenosis in artery stents. Labelling with 18F or 68Ga allows molecular imaging using positron emission tomography (PET) in animals and man. Thus, the varying integrin patterns of different cancers can be elucidated, a prerequisite for personalized medicine.
A similar procedure as described for the RGD peptides was applied to the chemokine receptor CXCR4 leading to a superpotent ligand for anti-HIV therapy and to the first imaging of cancer by targeting this receptor.
Recent publications:
S. Neubauer, F. Rechenmacher, A. J. Beer, F. Curnis, K. Pohle, C. D´Alessandria, H.-J. Wester, U. Reuning, A. Corti, M. Schwaiger, H. Kessler, Selective imaging of the angiogenic relevant integrins α5β1 and αvβ3, Angew Chem.Int. Ed. 2013, in press.
F. Rechenmacher, S. Neubauer, J. Polleux, C. Mas-Moruno, M. De Simone, E. A. Cavalcanti-Adam, J. P. Spatz, R. Fässler, H. Kessler, Functionalizing αvβ3- or α5β1-Selective Integrin Antagonists for Surface Coating: A Method to Discriminate Integrin Subtypes In Vitro, Angew. Chem. Int. Ed. 2013, 52, 1572-1575.
O. Demmer, A.O. Frank, F. Hagn, M. Schottelius, L. Marinelli, S. Cosconati, R. Brack-Werner, S. Kremb, H.-J. Wester, H. Kessler; A Conformationally Frozen Peptoid Boosts CXCR4 Affinity and Anti-HIV Activity, Angew Chem. Int. Ed. 2012, 51, 8114-8117.
A similar procedure as described for the RGD peptides was applied to the chemokine receptor CXCR4 leading to a superpotent ligand for anti-HIV therapy and to the first imaging of cancer by targeting this receptor.
Recent publications:
S. Neubauer, F. Rechenmacher, A. J. Beer, F. Curnis, K. Pohle, C. D´Alessandria, H.-J. Wester, U. Reuning, A. Corti, M. Schwaiger, H. Kessler, Selective imaging of the angiogenic relevant integrins α5β1 and αvβ3, Angew Chem.Int. Ed. 2013, in press.
F. Rechenmacher, S. Neubauer, J. Polleux, C. Mas-Moruno, M. De Simone, E. A. Cavalcanti-Adam, J. P. Spatz, R. Fässler, H. Kessler, Functionalizing αvβ3- or α5β1-Selective Integrin Antagonists for Surface Coating: A Method to Discriminate Integrin Subtypes In Vitro, Angew. Chem. Int. Ed. 2013, 52, 1572-1575.
O. Demmer, A.O. Frank, F. Hagn, M. Schottelius, L. Marinelli, S. Cosconati, R. Brack-Werner, S. Kremb, H.-J. Wester, H. Kessler; A Conformationally Frozen Peptoid Boosts CXCR4 Affinity and Anti-HIV Activity, Angew Chem. Int. Ed. 2012, 51, 8114-8117.
Practical information
- General public
- Free
Organizer
- Prof. Jieping Zhu, [email protected] and Prof. Christian Heinis, [email protected]
Contact
- Prof. Jieping Zhu, [email protected] and Prof. Christian Heinis, [email protected]