FLUOR MMPI: Selective fluorinated inhibitors of matrix metalloproteinases 3 and 9

• Unité de recherche: PCRD EU
• Numéro de projet: 01.0282
• Titre du projet anglais: FLUOR MMPI: Selective fluorinated inhibitors of matrix metalloproteinases 3 and 9

Mots-clé (Anglais)

Education; Training; Scientific Research; Social Aspects

Autre Numéro de projet (Anglais)

EU project number: HPRN-CT-2002-00181

Programme de recherche (Anglais)

EU-programme: 5. Frame Research Programme - 4.1.1 Research training networks

Description succincte (Anglais)

See abstract

Autres indications (Anglais)

Full name of research-institution/enterprise:
ETH Zürich
Institut für Pharmazeutische Wissenschaften
ETH Hönggerberg, HCI G 396.4

Résumé des résultats (Abstract) (Anglais)

Heart failure and cancer are the two major causes of death in developed countries. Current therapies for their cure are affected by largely unsolved problems. A common feature of both pathologies is that matrix metalloproteinases (MMPs) 3 and 9, which are zinc-dependent proteolytic enzymes, play a key role. Inhibitionof MMPs 3 and 9 is promising for heart failure and cancer therapy, but the currently available inhibitors are poorly selective, and therefore toxic. The primary objective of this project is to discover novel families of inhibitors selective for MMPs 3 and 9 from fluorinated peptidomimetic units. This challenging goal will be pursued by exploiting the potent tools made available by a synergistic and multisciplinary collaboration encompassing all aspects of drug discovery, including fluorine/asymmetric/combinatorial chemistry, structural chemistry, modelling, protein crystallography, pharmacology, physiology and biology, with the additional support of an industrial partner. The other main objective of this research project is to provide an effective training for young scientists at the interface of chemistry and biology in a very competitive international context where discovery of new drugs rests mainly on the ability to use complementary approaches from various disciplines and expertises.

Eventually, the scientific achievements stemming from this project will improve our knowledge of a variety of timely and fundamental topics such as:
1) the asymmetric/combinatorial synthesis of chiral fluorinated peptides and mimetics;
2) the mechanism of action of MMPs;
3) the behaviour of fluorine-containing functions in the enzyme active sites, as well as of their influence on the recognition of the ligand by the enzymes and the effect on the binding affinity;
4) the in vivo tests of the fluorinated inhibitors, and;
5) the generation of human monoclonal antibodies against MMP-3 and MMP-9.

Références bases de données (Anglais)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 01.0282