Funding

Project finished. Theme: Very high-density peptide arrays by particle manipulation in liquid phase

The invention of particle-based combinatorial synthesis of peptide arrays by KIT opened a new avenue to high-density peptide arrays. Briefly, amino acid monomers are incorporated into particles within a solid polymer matrix. These particles can be addressed to spatially defined areas. By melting these particles, amino acids are freed to diffuse to the surface of the solid array support and couple there to free amino groups. Afterwards, uncoupled amino acid particles and polymer matrix will be washed out. Thus, deposited particle patterns result in patterns of coupled amino acids. Repeating of the particle patterning and coupling processes leads to formation of spatially defined different peptide spots assembled in array format. The spot density of the peptide arrays depends on the density of particle patterns. We want to jointly adopt selective laser manipulation of particles for our particle-based peptide synthesis. By emulsifying our amino acid particles within water, we should be able to construct an especially simple, yet fully automated machine to generate high density peptide arrays. Additionally, we will adopt novel optically responsive nanoparticle surfaces to facilitate label-free in situ detection of binding kinetics and low affinity binding events. This evolutionary approach based on molecular diversity and on selection in array format might indeed advance basic science due to efficient screening for molecules with desired properties.

Partners:

Prof. Dr Alexander Nesterov-Müller, Project Speaker, Karlsruhe Institute of Technology

Prof. Dr. Reiner Dahint, University of Heidelberg, Applied Physical Chemistry

Dr. Olga Baum, The Institute on Laser and Information Technologies of the Russian Academy of Sciences

Project finished. Theme: Combinatorial Patterning of Particles for High Density Peptide Arrays

Duration: 11/2011 - 10/2016; EU Contribution: 1.5 M€

Summary

The ERC project “COMBIPATTERNING” is focused on the combinatorial deposition of monomers for the solid phase peptide synthesis in high density array format. We have developed two different methods to pattern amino acids. The first one uses laser radiation that transfers tiny amounts of polymer matrix with embedded monomers on the synthesis slides. The advantage of this procedure is that the coupling of the amino acids starts by heating synthesis slides for all amino acids simultaneously. Only one coupling cycle is needed for all 20 proteogenic amino acids. A special feature of this method is that the monomers and other reactants on the synthesis slide are located embedded in nanolayers and can mix with each other. It enables the screening not only for molecules synthesized but also for different reaction conditions, for instance for activation reactants. The second method is called stochastic arrays and based on the self-organization of particles in micro cavities. The stochastic arrays have in principle no limits in terms of spot pitch and can be downscaled to the single molecule stochastic arrays. This is remarkable step in combinatorial chemistry that can be extended to all kinds of the solid phase reactions. These novel arrays enable readout of information saved in human serum and design of novel molecular architectures in evolutionary manner.

Theme: Peptide arrays as a high throughput prescreening tool

In the current project, we want to verify the innovation potential of our novel stochastic peptide arrays that should find a market in all kinds of applications where pre-screening of large peptide libraries is done.