ORGN 649 |
| In de novo protein design one attempts to create artificial proteins with defined structure and function from first principles, usually with the help of trial-and-error procedures that scan a large number of possible amino acid sequences. Our approach to de novo protein design is based on peptide dendrimers. Dendrimers are tree-like structures that adopt a globular or disk-shaped structure as a consequence of topology rather than folding. Our peptide dendrimers are obtained by alternating alpha-aminoacids with branching diaminoacids. Dendrimers containing combinations of histidine, serine and aspartate display enzyme-like catalytic properties for the hydrolysis of esters, including enantiomeric discrimination. The catalytic effect involves cooperative substrate binding and catalysis by a positive dendritic effect. We have now developed a combinatorial approach enabling the preparation of libraries containing over 60'000 different peptide dendrimers. A protocol was established for screening the beads for catalytic turnover and determining the dendrimer sequence on single resin beads. Screening of a combinatorial peptide dendrimer library leads to peptide dendrimers with esterase activity. The library approach was also used to discover peptide dendrimers with binding affinity to ligands. Peptide dendrimer libraries provide a new and versatile source of artificial proteins acting as functional supramolecular systems for molecular recognition and chemical catalysis. Recent data relating to the selection and properties of enantioselective catalytic peptide dendrimers and ligand-binding dendrimers will be discussed.
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Proteins, Peptides, and Nucleotides
8:00 AM-11:00 AM, Wednesday, 16 March 2005 Convention Center -- Room 9, Oral
Division of Organic Chemistry |
