Selective molecular recognition of beta-sheets

This dissertation presents three studies on cross-strand amino-acid pairing energies using mixtures of model beta-sheet peptides, and one study on the synthetic progress toward another beta-sheet model, beta-sheet sandwich.;Part I of this dissertation describes the development of a model system, beta-sheet peptide, which allows the studies of amino-acid pairing preferences. Pairing studies involve water-like amino acids (Thr and Ser) and oil-like amino acid (Val) showed molecular recognition of beta-sheets is sequence selective. This pairing study showed homogeneous pairings (water-like with water-like and oil-like with oil-like) is preferred by 0.2--0.4 kcal per mol per pair. These results showed that beta-sheet peptides are suitable for pairing studies.;This dissertation then describes pairing studies that involve amino acid with hydrocarbon side chains (Ala, Val, Leu, Phe, Cha, and Ile). This study showed specific pairing preference (0.1 kcal per mol per pair) between amino acids with hydrocarbon side chains. Molecular modeling and variable-temperature studies suggest the shape of amino-acid side chain influences the pairing preference.;This dissertation concludes Part I by describing the pairing studies that involve two enantiomeric amino acids. This study showed amino-acid pairings are enantioselective, and homochiral pairings (L-L and D-D) preferred over heterochiral pairings (L-D ) by 0.6--0.8 kcal per mol per pair.;Part II of this dissertation describes the synthetic studies toward of an artificial beta-sheet sandwich comprising two beta-sheets that are held together by a template and an additional molecular strap.