beta-sheet peptide architecture: Measuring the relative stability of Parallel vs. Antiparallel beta-sheets

摘要

Among the most commonly occurring protein secondary structures, beta-sheets are the least studied because well-characterized peptide medel systems are not available. Im particular despite a number of theoretical studies implication the possible role of amino acid residues and cross-strand interactions between side chains in directing the folding characteristics of beta-sheet structures, to date no direct experimental evidenee has been forthcoming to establish the underlying energetic factors that mayfavor the formation of parallel or antiparallel arrangements. Here we describe the design, synthesis, and characterization of a novel model structure for beta-sheets and provide the first direct evaluation of the thermodynamic preference for the an-tiparailel vs. parallel beta-sheet formation. Within the constraints of the present model, our studies establish for the first time the significant role of backbone-backbone hydrogen-bonding interactions in favoring the formation of the antiparallel beta-sheet structure.