The conformation of oligomers of beta-amino acids of the general type Ac-[beta-Xaa]n-NHMe (beta-Xaa = beta-Ala, beta-Aib, and beta-Abu; n = 1-4) was systematically examined at different levels of ab initio molecular orbital theory (HF/6-31G*, HF/3-21G). The solvent influence was considered employing two quantum-mechanical self-consistent reaction field models. The results show a wide variety of possibilities for the formation of characteristic elements of secondary structure in beta-peptides. Most of them can be derived from the monomer units of blocked beta-peptides with n = 1. The stability and geometries of the beta-peptide structures are considerably influenced by the side-chain positions, by the configurations at the C alpha- and C beta-atoms of the beta-amino acid constituents, and especially by environmental effects. Structure peculiarities of beta-peptides, in particular those of various helix alternatives, are discussed in relation to typical elements of secondary structure in alpha-peptides.

A systematic quantum chemical study on the structure and stability of the major types of β‐turn structures in peptides and proteins was performed at different levels of ab initio MO theory (MP2/6‐31G*, HF/6‐31G*, HF/3‐21G) considering model turns of the general type Ac(SINGLE BOND)Xaa(SINGLE BOND)Yaa(SINGLE BOND)NHCH3 with the amino acids glycine, l‐ and d‐alanine, aminoisobutyric acid, and l‐proline. The influence of correlation effects, zero‐point vibration energies, thermal energies, and entropies on the turn formation was examined. Solvent effects on the turn stabilities were estimated employing quantum chemical continuum approaches (Onsager's self‐consistent reaction field and Tomasi's polarizable continuum models). The results provide insight into the geometry and stability relations between the various β‐turn subtypes. They show some characteristic deviations from the widely accepted standard rotation angles of β turns. The stability order of the β‐turn subtypes depends strongly on the amino acid type. Thus, the replacement of l‐amino acids in the two conformation‐determining turn positions by d‐ or α,α‐disubstituted amino acid residues generally increases the turn formation tendency and can be used to favor distinct β‐turn subtypes in peptide and protein design. The β‐turn subtype preferences, depending on amino acid structure modifications, can be well illustrated by molecular dynamics simulations in the gas phase and in aqueous solution. © 1997 by John Wiley & Sons, Inc. J Comput Chem 18: 1415–1430, 1997

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Novel semiempirical methods (OM1, OM2) have been employed to study typical elements of secondary structure in peptides and proteins. The calculated geometries and relative stabilities are discussed in comparison to corresponding data from the ab initio MO theory and from the established semiempirical methods AM1 and PM3, respectively. It is shown that the description of the peptide conformers is considerably improved by OM1 and OM2 compared with AM1 and PM3, although in some cases there are still discrepancies with the ab initio data.

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The first total synthesis of Hypomurocin A1 (HM A1) in solution phase is described. As members of the peptaibol family, hypomurocins are constituted by two groups of peptides: six undecapeptides (undecamers) in the HM A group and six octadecapeptides (18-mers) in the HM B group. The synthesis presented has been successfully achieved by the 'azirine/oxazolone method' to introduce the two Aib-Pro sequences included in this undecapeptaibol in one step with methyl 2,2-dimethyl-2H-azirine-3-prolinate as the building block. The coupling reactions of the Z-protected amino acids or peptide acids involved the use of N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) and 1-hydroxybenzotriazole (HOBt), and led to the peptides in good-to-very-good yields. The peptides were purified by reverse-phase HPLC and characterized by NMR spectroscopy (1H, 13C, COSY, TOCSY, HSQC, HMBC, ROESY), ESI-MS, IR, elemental analysis, optical rotation, and X-ray crystallography. An NMR analysis of HM A1 was also carried out in deuterated micelles to perform a structural comparison of the helix in solution and in membranes.