Multifunctional peptide polymers for the efficient modulation of intracellular signal transduction

• Applicants: Professor Dr. Roland Brock; Professor Dr. Jörg Rademann
• Subject Area: Biological and Biomimetic Chemistry
• Term: from 2006 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 28198074

In cellular signal transduction, molecular interactions mediated by linear peptide motifs play a major role. In vitro, peptides corresponding to these motifs act as specific inhibitors of these interactions. Given the lack of chemical inhibitors interfering with molecular interactions, these peptides represent a valuable tool for analyzing the role of molecular interactions in cellular signal transduction. However, at present the intracellular application of peptides is hampered by poor bioavailability and limited stability. Within this project, multifunctional peptide polymers will be synthesized, analyzed and investigated for the efficient modulation of cellular signaling. The multifunctional peptide polymers will combine three properties: (i) Efficient cellular up-take, (ii) rapid release into the cytoplasm and (iii) stabilization of the functional peptides. For this purpose, several peptide entities mediating these functions will be coupled to various polymers via oxime ligation. The stoichiometry of the individual functional signals on the polymers will be analyzed following to the ligation reaction; precise control of the stoichiometry and the spatial arrangement of functional signals will be granted by using a dendritic branching approach. The results of this project will enable the in-depth analysis of specific molecular interactions in cellular signaling networks.

• DFG Programme: Research Grants
• International Connection: Netherlands