Stereochemical control of hairpin formation in beta-peptides containing dinipecotic acid reverse turn segments

We examine the relationship between covalent structure and conformational p ropensity among a series of beta-amino acid tetramers. These experiments fo cus on the hairpin folding motif. Among conventional peptides, the minimum increment of beta-sheet secondary structure is a "beta-hairpin," in which t wo strands are connected via a short loop. The present studies are aimed at optimizing hairpin stability among beta-peptides. Previous work from our l aboratory has identified optimal substitution patterns for residues that fo rm strands in an antiparallel beta-peptide sheet (Krauthauser et al. J. Am. Chem. Sec. 1997, 119, 11719), and we have shown that a dinipecotic acid se gment can promote sheet-type interactions between attached strand residues (Chung et al. J. Ant. Chem. Sec. 1998, 120, 10555). Here we compare all fou r possible configurations of the dinipecotic acid segment, (R,S), (S,R), (R ,R) and (S,S), for the ability to induce sheet formation with a constant se t of enantiomerically pure strand residues. We show that both heterochiral dinipecotic acid segments promote hairpin formation, although one is distin ctly superior. Neither of the homochiral dinipecotic acid supports hairpin folding. When the strand residues are beta-alanine (achiral), the heterochi ral dinipecotic acid segment is again superior to the homochiral segment, b ut we find a difference between hairpin conformations in solution and in th e solid state.