This research is directed toward synthesis and derivatization of novel DNA-binding peptides and detailed characterization of their DNA-binding and -condensing properties. A series of low molecular weight branched oligolysines and oligoarginines with a defined coupling site will be synthesized. We will determine the effect of number and positioning of positive charges on DNA condensation. Selected compounds will be derivatized with effectors such as receptor ligands, membrane-destabilizing peptides, carbohydrates and PEG. DNA binding properties of the various derivatives and the physical characteristics of resulting DNA complexes will be examined. Considering parameters like hydrophobicity and propensity of amino acids for particular secondary structures, we will introduce a limited number of rational mutations into a known membrane-destabilizing hexapeptide sequence and select peptides with highest membrane-destabilizing activities. The dependence of transfection efficiency in cell culture on DNA complex composition will be examined. Using the GCG package, membrane destabilizing peptides have been selected and compared for their primary, secondary and tertiary structure. This information and things like hydrophobicity indices etc. are essential in finding and designing new peptide sequences for the above-described project. The facilities provided by the Computer Graphics Laboratory are absolutely necessary for the continuation of this work. GL
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