Enantiomerically pure beta-amino acid derivs. with the side-chains of Ala, Val, and Leu in the 2- or 3-position (β2- and β3-amino acids, resp.), as well as with substituents in both the 2- and 3-positions (β2,3-amino acids, of like-configuration) were prepd. and incorporated into β-hexa-, β-hepta-, and β-dodecapeptides. The new and some of the previously prepd. beta-peptides showed NH/ND exchange rates (in MeOH at room temp.) with tau1/2 ? 60 days, unrivaled by short-chain alpha-peptides. All beta-peptides were designed to be able to attain the previously described 31-helical structure. CD measurements, indicating a new secondary structure of certain beta-peptides constructed of beta2- and beta3-amino acids, were confirmed by detailed NMR soln.-structure anal. A beta2-heptapeptide and a beta2,3-hexapeptide have the 31-helical structure, while to a beta2/beta3-hexapeptide with alternating substitution pattern H-(beta2-Xaa-beta3-Xaa)3-OH a novel, unusual helical structure (in (D5)pyridine and in CD3OH) was assigned, with a central 10-membered and 2 terminal 12-membered H-bonded rings, and with C:O and N-H bonds pointing alternatively up and down along the axis of the helix. Thus, two types of beta-peptide turns were identified in soln. Hydrophobic interactions of and hindrance to solvent accessibility by the aliph. side-chains are discussed as possible factors influencing the relative stability of the two types of helixes.
Nako Nakatsuka, Xinyu Zhang, Haiying Hu
Jérôme Waser, Christine Alice Jacqueline Marty, Emmanuelle Madeline Dominique Allouche