Zipper-featured delta-peptide foldamers driven by donor--acceptor interaction. Design, synthesis, and characterization.

Abstract

Donor-acceptor interaction between electron-rich 1,5-dioxynaphthalene (DAN) and electron-deficient pyromellitic diimide (PDI) has been utilized to induce the formation of a new kind of zipper-featured delta-peptide foldamers. Seven l-ornithine-based delta-peptides 1a-g, in which one to three DNA and PDI units are incorporated to the two ends of the peptide backbones, respectively, have been designed and prepared by the standard liquid-phase synthetic method. (1)H NMR, UV-vis, and fluorescent quenching studies reveal that all the delta-peptides adopt folding conformations in nonpolar chloroform and polar DMF as a result of intramolecular donor-acceptor interaction between the DAN and PDI units. The folding states become more compact for the peptide skeletons possessing more donor-acceptor interacting sites. Variable-temperature UV-vis experiments indicate that, although the folding is a dynamic process, the folding state can remain even at 150 degrees C in DMF. Circular dichroism (CD) investigations reveal that the new generation of delta-peptides have similar folding patterns. A zipper-featured folding motif has been proposed for the new generation of delta-peptide foldamers. Molecular modeling has generated two most stable folding states for the longest delta-peptide 1g, with an energy difference of 26.80 kcal/mol.