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Structural & dynamical characterization of the pro-metastatic enzyme heparanase for the designing of novel inhibitors

Ziel

The focus of the project is the understanding of the biological functions and the structural characterization of heparanase. Heparanase is an endo-b-D-glucosidase capable of specifically degrading heparan sulfate, one of the extracellular matrix (ECM) components. This activity is associated with the metastatic potential of tumor cells, because these cells require the ability to degrade the ECM. During the last decade, NMR spectroscopy has become a leading technique to study biomolecules. Nowadays, its versatility allows the three-dimensional structure determination of biological macromolecules, the characterization of protein dynamics, kinetic and thermodynamic information on protein folding, as well as on molecular interactions.

This last issue has revealed NMR as an important tool for the Drug Discovery. The major limitation of NMR arises from the increase of transverse relaxation rates which prevents the investigation of molecules with large molecular weights. Heparanase is initially expressed as a 543 aminoacid polypeptide (65 kDa). The study of a protein of this size represents a challenge for NMR methodologies currently available.

Wissenschaftliches Gebiet (EuroSciVoc)

Thema/Themen

Aufforderung zur Vorschlagseinreichung

FP6-2004-MOBILITY-11
Andere Projekte für diesen Aufruf anzeigen

Finanzierungsplan

ERG - Marie Curie actions-European Re-integration Grants

Koordinator

CENTRO DE INVESTIGACIÓN PRÍNCIPE FELIPE
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