β(2)- and β(3)-peptides with proteinaceous side-chains. Synthesis and solution structures of constitutional isomers, a novel helical secondary structure, and the influence of solvation and hydrophobic interactions on folding
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.
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Seebach, D., Abele, S., Gademann, K., Guichard, G., Hintermann, T., Jaun, B., Matthews, J. L., Schreiber, J. V., Oberer, L., Hommel, U., & Widmer, H. (1998). β(2)- and β(3)-peptides with proteinaceous side-chains. Synthesis and solution structures of constitutional isomers, a novel helical secondary structure, and the influence of solvation and hydrophobic interactions on folding. Helvetica Chimica Acta, 81(5), 932–982. https://doi.org/10.1002/hlca.19980810513
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