Selective sugars Interactions with peptide receptors: gas phase Models and Pharmaceutical Applications – SIMPA

Sugar - protein interactions are crucial for the development of new drugs that interact specifically with their therapeutic targets. Photodynamic therapy (PDT) strategies use Mannose-decorated photosensitizers (PS) to target Mannose Receptor Proteins (MRP) overexpressed on tumor cells. A priority in the design of new PS is to improve the specificity of their interaction with MRP.
The SIMPA project brings together specialists in gas phase spectroscopy, in surface science applied to pharmaceutical systems, in molecular modeling of large size biomolecular systems, and organic chemists. We propose complementary physicochemical approaches to study the molecular interactions between mannose and MRP exploited in targeted PDT. The molecular systems we will study range from small gas phase models to real pharmaceutical systems.
In the gas phase we will study the structure of complexes containing PS and MRP models inspired by natural binding sites, either completely isolated or interacting with a few water molecules. Gas-phase conformation-selective, vibrationally-resolved laser spectroscopy will uniquely probe local molecular interactions and the structural role of water.
In the solvated phase, the global interaction between PS and MRP, deposited in artificial membranes, will be studied by atomic force microscopy (AFM) and quartz crystal microbalance and dissipation (QCM-D), and NMR measurements. These experiments will provide key information on the affinity, strength and selectivity of the interaction for different arrangements of CBH on the PS and for different MRPs.
Molecular modeling will help to interpret, complete and bring together the results of studies in the gas phase, on artificial membranes and in solution.