Comparison of the effect of five guest residues on the beta-sheet conformation of host (L-Val)n oligopeptides

The synthesis, characterization, and IR absorption, 1H NMR, and CD properties of (L-Val)n host tetra-, penta-, and hexapeptides contaioning an L-Ile, L-Ala, D-Val, L-Pro, or Aib guest resides are reported, with the intention of establishing a scale of beta-sheet disrupting capability of various amino acids. The results indicate that in the solid state the beta-sheet structures of the (L-Val)n (n=5,6) homopeptides are at least partially disrupted by the L-Pro and Aib residues. In CH2Cl2/Me2SO solvent mixtures the following rank order is obtained for the stability of the beta-sheets: L-Val > L-Ile >> L-Ala >> D-Val > L-Pro >> Aib. In CDCl3 solutions the Aib hexapeptide is folded into a partially labile 3(10)-helical structure. Statistically disordered conformations largely prevail in more polar solvents like 2,2,2-trifluoroethanol and ethanol in all the peptides examined. Only the (L-Val)n hexapeptide is prone to adopt the beta-sheet conformation upon addition of 40% (v/v) water to the trifluoroethanol solution.