Towards a toolkit of distinctly folded biomimetic oligomers

ORGN 62

Paramjit S. Arora, arora@nyu.edu, Department of Chemistry, New York University, 100 Washington Square East, New York, NY 10003
We are developing a toolkit of protein secondary structure mimetics and other distinctly folded biomimetic oligomers as potential modulators of specific biomolecular interactions. Proteins typically utilize small folded domains for recognition of other biomolecules. The basic hypothesis guiding our research efforts is that by mimicking these folded domains, we can reproduce the function of a particular protein with metabolically stable synthetic molecules. This talk will discuss two general methods for the preparation of such biomimetic scaffolds. One method involves stabilization of peptides into desired helical folds (alpha, 3(10), or pi) by substitution of a main-chain hydrogen bond with a covalent bond. The second approach involves generation of nonpeptidic scaffolds by replacement of amide bonds with heteroaromatic rings capable of influencing the resulting oligomer into a defined conformation. These two approaches provide us with unique scaffolds to target chosen protein receptors and nucleic acids.