An Artificial β-Sheet That Dimerizes through Parallel β-Sheet Interactions

Abstract

This Article introduces a simple chemical model of a β-sheet (artificial β-sheet) that dimerizes by parallel β-sheet formation in chloroform solution. The artificial β-sheet consists of two N-terminally linked peptide strands that are linked with succinic or fumaric acid and blocked along one edge with a hydrogen-bonding template composed of 5-aminoanisic acid hydrazide. The template is connected to one of the peptide strands by a turn unit composed of (S)-2-aminoadipic acid (Aaa). ¹H NMR spectroscopic studies show that these artificial β-sheets fold in CDCl₃ solution to form well-defined β-sheet structures that dimerize through parallel β-sheet interactions. Most notably, all of these compounds show a rich network of NOEs associated with folding and dimerization. The compounds also exhibit chemical shifts and coupling constants consistent with the formation of folded dimeric β-sheet structures. The aminoadipic acid unit shows patterns of NOEs and coupling constants consistent with a well-defined turn conformation. The present system represents a significant step toward modeling the type of parallel β-sheet interactions that occur in protein aggregation.