Stereo-Controlled Supramolecular Assembly of 4(R/S)-Aminoproline Based Peptides and Peptide Nucleic Acids

Abstract

The thesis entitled “Stereo-Controlled Supramolecular Assembly of 4(R/S)-Aminoproline Based Peptides and Peptide Nucleic Acids” is comprised of studies on design, synthesis of peptides and peptide nucleic acids containing 4(R/S)-aminoproline and its derivatives, and studies on their conformational properties and self-assembling properties. The work explores the solvent dependent and stereo-specific PP-II - β conformational transitions exhibited by 4(S)-aminoprolyl polypeptides, and their assembly into slender nanofibers with left-handed twists. The effect of lipidation and, of replacing C4(R/S)-NH2 with guanidine, on the conformational preference of the polypeptides is investigated. The consequences of these modifications on the morphology of the peptide assemblies are also probed. In order to utilize the rich conformational dynamics of 4(R/S)-aminoproline to generate complex self-assembled structures, branched polyproline peptides and branched peptide nucleic acids were synthesized with the trifunctional amino acid, 4(R/S)-aminoproline as chiral branching core. The conformational and self-assembly studies show that a variety of complex supramolecular assemblies can be constructed with these motifs. Moreover, under specific conditions, stereo-control over morphology of self-assembled structures can be achieved by altering the stereochemistry at the C4 position of aminoproline.