STRUCTURAL STUDIES ON THERAPEUTICALLY RELEVANT PROTEINS DRUG DISCOVERY IMPLICATIONS

1 MULTIPLE ALIGNMENTS FOR STRUCTURAL FUNCTIONAL OR PHYLOGENETIC ANALYSES
11 KARIN KNOTTENBAUER – MODELLING INNOVATION AND STRUCTURAL CHANGE
1212014 APPLICANT’S NAME STRUCTURAL SEE FAA ORDER 811037 APPENDIX

20 THE STRUCTURALIST CONCEPTION OF OBJECTS ANJAN CHAKRAVARTTY
205 COMMON STRUCTURAL ELEMENTS COMMON STRUCTURAL ELEMENTS
3 CUMPLIMIENTO DEL CTE 31 SEGURIDAD ESTRUCTURAL HOJA NÚM

STRUCTURAL STUDIES ON THERAPEUTICALLY RELEVANT PROTEINS

STRUCTURAL STUDIES ON THERAPEUTICALLY RELEVANT PROTEINS: DRUG DISCOVERY IMPLICATIONS


Antonio Pineda-Lucena, Rodrigo J. Carbajo, David Pantoja-Uceda, Cheryl Hawkins, Ana M. Fernández-Escamilla, Silvia Mosulén, Leticia Ortí


Laboratorio de Biología Estructural, [email protected], Centro de Investigación Príncipe Felipe, Avda. Autopista del Saler 16-3, Valencia-46013, Spain



NMR spectroscopy is a versatile biophysical technique with wide applicability in drug discovery research, particularly for the detection and characterization of molecular interactions. In general, biomolecular NMR plays a very important role at the different stages of the drug discovery program: target selection, hit identification, and lead optimization. Furthermore, its role is becoming increasingly important in pharmacokinetic and pharmacodynamic profiling of compounds.

A potential drug target is defined as a protein with a propensity to bind small molecules that modulate its activity (drugable target) and with the potential to be disease modifying. In any case, a prerequisite for initiating structural studies is to obtain protein in enough quantity for NMR characterization. This is probably one of the main "bottlenecks" of the whole process, since it is imperative to produce proteins in a stable and soluble form.

Our laboratory is interested in the structural elucidation of therapeutically relevant proteins, and in the identification of small molecule modulators of their activity. In order to do that, we use NMR in combination with computational chemistry and biochemistry approaches.

In this presentation, I will review some of the projects we are working on at this time, like our efforts to understand the role that solvent-exposed residues play in the stability of proteins using p53 tetramerization domain as a model, the design of peptide models to obtain a deeper insight into protein-protein interactions, the structural characterization of disintegrins, and our initial results on heparanase, an enzyme involved in the degradation of the extracellular matrix, which plays a key role in metastasis.


3 ELEMENTARY LESSON PLAN (STRUCTURAL APPROACH) RECOGNIZING COMMUNITY SETTINGS
31303 PRECAST AND PRESTRESSED CONCRETE STRUCTURAL MEMBERS THE STANDARD
5 ALUMINUM STRUCTURAL PLATE SPECIFICATIONS 10 GENERAL 11 THIS


Tags: discovery implications, drug discovery, therapeutically, implications, structural, discovery, studies, proteins, relevant