Zipper-Featured δ-Peptide Foldamers Driven by Donor-Acceptor Interaction. Design, Synthesis, and Characterization

摘要

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 δ-peptide foldamers. Seven L-ornithine-based δ-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. ~1H NMR, UV- vis, and fluorescent quenching studies reveal that all the δ-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 ℃ in DMF. Circular dichroism (CD) investigations reveal that the new generation of δ-peptides have similar folding patterns. A zipper-featured folding motif has been proposed for the new generation of δ-peptide foldamers. Molecular modeling has generated two most stable folding states for the longest δ-peptide 1g, with an energy difference of 26.80 kcal/mol.