W0337

Metal Ion Control of the Activity of Oligopeptide Foldamers. Paolo Scrimin, University of Padova, Department of Organic Chemistry and CNR-CMRO, 35131-Padova Italy (scrimin@mail.chor.unipd.it).

The use of the peptide framework as an excellent scaffold for the obtainment of supramolecular structures has spurred increasing interest in the control of the conformation of peptides and in the synthesis of new amino acids. The final goal is the effective positioning of functional groups or appropriate subunits in key relative position to trigger, in the supramolecular architecture of the polypeptide, new functions. Furthermore, the modular synthetic strategy towards the synthesis of oligo- and polypeptides is prone to combinatorial selection of the new systems.

Our approach to the above targets is either to use C⁽-tetrasubstituted amino acids to impose conformational constraint in the sequence to elicit helical conformations already with very short sequences or to introduce metal ion binding sites to modulate the geometric arrangement in the space of the oligomeric constituents.

Following the strategies outlined above we have prepared: a) short foldamers in which we have introduced at least two copies of a functional amino acid with the precise objective of inducing cooperativity between the functional groups for catalytic purposes; b) short peptides assembled on a template (Au nanoparticles or polyamines) for molecular recognition or supramolecular catalysis. Examples that will be discussed in detail will be those constituted by: i) heptapeptides incorporating two copies of a new metal-coordinating amino acid that proved to be good catalysts of the cleavage of a RNA-model substrate and DNA as well (see J. Am. Chem. Soc. 1999, 121, 6948, J. Am. Chem. Soc. 2001 in press, and structure 1); ii) a polypeptide template modeled after the C- and N-terminal residues of each monomer of HIV-1 protease (see structure 2) for the allosteric regulation of the activity of the enzyme.