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Probing Hierarchical Self-Assemblies Relevant for Drug and Vaccine Design by Employing Scanning Tunnelling Microscopy

Fachliche Zuordnung Biologische und Biomimetische Chemie
Förderung Förderung von 2006 bis 2011
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 24839738
 
The interactions of oligosaccharides with carbohydrate-binding proteins are of relevance to the function of drugs and vaccines. A part of the oligosaccharide guest molecule fits into a binding pocket of the carbohydrate-binding host molecule, but only weak interactions are responsible for this attraction. Binding of the carbohydrate guest usually results in a change of conformation of the host. Only little is known of these interactions. An increased understanding of host-guest assemblies through new scanning probe methods can suggest new ways of drug and vaccine design and production. We will design molecular systems, which can be attached to surfaces (e.g. graphite) and studied in single molecule resolution with scanning probe methods. An exemplary host-guest interaction, nonamannose molecules (found modified in the gp120 protein on the exterior of HIV virus), will be assembled on the graphite substrate by surface adaptor molecules (first level of assembly by weak interactions). This initial step of assembly, which controls the spacing (and thus protein-protein interaction) and prevents unintended protein substrate interactions, can be monitored by scanning tunneling microscopy (STM). Following this assembly, the cyanovirin-N host protein (found in the exterior of a unicellular alga, which is known to hinder virus-cell fusion of the HIV virus) will be introduced and through key-lock interaction with the saccharide-guest will eventually change conformation (second and third level of assembly by weak interactions). Relevant data will be retrieved by atomic force microscopy (AFM) and STM techniques. Later this technique will be applied to unknown protein-carbohydrate interactions. Rather than in an ensemble with regular diffraction methods, new interaction processes and dynamics may be accessed on the single molecule level. Theoretical modeling, performed with state of the art DFT and TDDFT (input from many body perturbation theory and Greens´ function methods), will further our understanding of the observed interactions and assembly dynamics.
DFG-Verfahren Sachbeihilfen
Internationaler Bezug Schweiz, Spanien
 
 

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