FROM SECONDARY STRUCTURE ELEMENTS TO CATALYTIC SYSTEMS

The development of unnatural backbone oligopeptides capable of protein-like folding is the focus of intensive research efforts, due to the prospect of these molecules to deliver protein-like functions (e.g. biomolecular recognition, catalysis) on protease resistant backbone. I have stressed the importance of achieving tertiary structure in unnatural polypeptide as a prelude to developing sophisticated functions, but it must be pointed that short oligomers with discrete and predictable secondary structural preference are themselves potentially useful. One obvious application would be to use such molecules as catalyst support and transportation. In the course of our continuing study on conformational behaviour of D,L-alternating peptides [1] has been observed that substituting large hydrophobic constituent with other similar residues containing functional groups on the side chain show to have a minimal effect on the stability of secondary structure. Here we present de novo designed peptides that contains structural elements qualified for both stable helical folding as well as sheet formations as competing subunits. In order to obtain soluble, flexible, dimeric or trimeric structures we have synthetized and observed hetero-oligopeptides (i.e. composed of two or more types of monomer) with different length and compositions that can potentially assume a ?-sheet helical conformation. The balance between hydrogen bonds and hydrophobic interactions permit us to provide the conformational stability of the predicted structure(s). Interesting, norleucine oligopeptides form molecular aggregate that are unsoluble in organic solvents[2], whereas short sequences of L-isoleucine form soluble molecular aggregates in which the peptide chain assume the ?-conformation [3]. In this work we report about synthesis and conformational analysis of oligonorleucine peptides containing some leucine/isoleucine residues, with n=8-18 residues, having Boc-N- and -COOMe protected terminals. The result are discusses on the basis of steric and hydrophobic properties of the three side chain. References [1] Navarro E., Fenude E., Celda B., Biopolymers (2004) 73, 229-241 [2] Fenude Schoch E., Römer U.D., Lorenzi G.P., Int. J. Peptide Protein Res.(1994) 44, 10-18 [3] Lorenzi G.P., Paganetti T., J. Am. Chem. Soc.(1977) 104, 1282-83 [4] Saviano M. J. Am. Chem. Soc. (1995) 117, 8651-8658