Research Unit of Dr. Fiorella Meneghetti
X-Ray Crystallographic Laboratory
The X-Ray Crystallographic Laboratory located at the Department of Pharmaceutical Sciences seeks to understand the structure, function and interactions of important novel pharmaceutical derivatives at molecular level. The methods employed cover a range of techniques including X-Ray crystallography and neutron crystallography useful for the identification and geometric characterization of the compounds. The X-Ray data are collected on the locally available CAD4 Enraf-Nonius diffractometer (small molecule) or on the facilities at the ELETTRA synchrotron beamline (macromolecules). The laboratory is equipped for crystal growth optimization and protein crystallization screening techniques.
There are at the moment three areas of research:
- Structural biology of enzymes
- Structure-activity relationships of interesting pharmaceutical molecules
- Crystallography of lanthanide complexes for MRI.
1) Structural investigation of new STAT3 inhibitors
The general aim of the project is the design and identification of lead compounds useful for the development of new antitumor drugs, able to act efficaciously and selectively against appropriate target (STAT3), by organic synthesis methodologies. The X-Ray crystallography supports the understanding of biological activity of the new derivatives in relationship to their conformation. The project is carried out with the collaboration of KRIBB Institute (Taejon, Korea) and with the University of Shizuoka (Japan).
2) Structural studies on peptidomimetics
This research focus on the structural study of new peptidomimetics, in particular cyclic structures conformationally constrained, able to act as reverse beta-turn mimics. The new compounds are obtained through enantioselective synthesis of isochinolinic and piperidinic scaffolds. Their crystallographic structures are an important starting point for evaluating their ability to induce reverse turns in short bioactive peptides. The project aims to find efficient synthethic routes of new peptidomimetics having a specific biological target. The X-ray crystal structure of the new potential drugs is the first important step to relate the structure with the biological properties. The study of their conformational properties in the solid state is mainly interesting as this class of compounds is characterized by a high conformational freedom (in collaboration with Dr Alessandra Silvani, Dipartimento di Chimica, Università degli Studi di Milano, Dr Alessandro Sacchetti, Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano).
3) Structural characterization of lantanide complexes for MRI.
In the development of Lanthanide (III)-based contrast agents for Magnetic Resonance Imaging a great deal has been done to improve understanding of their physicochemical properties, which should allow a rational development of new agents. The potential of a Ln(III) complex to act as MRI Contrast Agents is strictly related to the property of the coordinated water molecule(s). The synthesis and characterization of new Ln(III) complexes based on the information gained by the X-Ray studies will be the aim of this project (in collaboration with Prof. S. Aime’s research group, University of Torino).