Role of Backbone Dipole Interactions in the Formation of Secondary and Supersecondary Structures of Proteins.

We present a generic solvated coarse-grained protein model that can be used to characterize the driving forces behind protein folding. Each amino acid is coarse-grained with two beads, a backbone, and a side chain. Although the backbone beads are modeled as polar entities, side chains are hydrophobic, polar, or charged, thus allowing the exploration of how sequence patterning determines a protein fold. The change in orientation of the atoms of the coarse-grained unit is captured by the addition of two oppositely charged dummy particles inside the backbone coarse-grained bead. These two dummy charges represent a dipole that can fluctuate, thus introducing structural polarization into the coarse-grained model. Realistic α/ß content is achieved de novo without any biases in the force field toward a particular secondary structure. The dipoles created by the dummy particles interact with each other and drive the protein models to fold into unique structures depending on the amino acid patterning and presence of capping residues. We have also characterized the role of dipole-dipole and dipole-charge interactions in shaping the secondary and supersecondary structure of proteins. Formation of helix bundles and ß-strands are also discussed.

Automating parallel peptide synthesis for the production of PNA library arrays.

A system was establishedfor the parallel synthesis of peptide library arrays in afully automated manner Synthesis takes place in blocks made of polyoxymethylene that hold during all synthesis steps a polypropylene membrane of 8 x 12 cm. Yields are in the nanomole range, obtained at a low consumption of reagents. The current setup is based on a commercially available pipetting robot and supports the generation of 1536 different oligomers/run. Much higher array densities are possible because the membranes are amicable to spot diameters of down to 200 microm, naturally at a cost of the absolute amount produced of each oligomer The method was put to use for the creation of arrayed libraries of peptide nucleic acids (PNAs). These can be employed both as a source of PNA molecules applied individually in experimentation subsequent to their release or as intact oligomer arrays in hybridization analyses.

Recent progress in oligonucleotide synthesis.

New blocking group combinations for the machine-aided oligoribonucleotide synthesis on solid phase material have been developed and tested regarding their general application. An acetal function for 2'-OH protection offers a series of advantages in the synthetic approach but special conditions have to be fulfilled in order to guarantee a selective cleavage of the temporary 5'-OH blocking group such as the dansylethoxycarbonyl or even the acid-labile dimethoxytrityl group in the chain elongation process. The final removal of the 2'-O-acetal function in the partially deblocked oligomer proceeds unexpectedly well under weak acidic conditions due to a supposed intramolecular acid catalysis.