A noncovalent approach to antiparallel β-sheet formation

Four tripeptide chains, when attached to the same end of a hydrogen-bonded duplex (1.2) with the unsymmetrical, complementary sequences of ADAA/DADD, have been brought into proximity, leading to the formation of four hybrid duplexes, 1a·2a, 1a·2b, 1b·2a, and 1b·2b, each of which contains a two-stranded β-sheet segment. The extended conformations of the peptide chains were confirmed by 1D and 2D NMR. The peptide strands stay registered through hydrogen bonding and the β-sheets are stabilized by side chain interactions. Two-dimensional NMR data also indicate that the duplex template prevents further aggregation in the peptide segment. When the peptide chains are attached to the two different termini of the duplex template, NMR studies show the presence of a mixture with no clearly defined conformations. In the absence of the duplex template, the tripeptides are found to associate randomly. Finally, isothermal titration calorimetry studies revealed that the hybrid duplex 1a·2a was more stable than either the duplex template or the peptides alone.