External chirality-triggered helicity control promoted by introducing a beta-Ala residue into the N-terminus of chiral peptides.

Department of Environmental Technology and Urban Planning, Shikumi College, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan.
Biomacromolecules (Impact Factor: 5.37). 01/2004; 5(4):1231-40. DOI: 10.1021/bm0344001
Source: PubMed

ABSTRACT The noncovalent chiral domino effect (NCDE), defined as chiral interaction upon an N-terminus of a 3(10)-helical peptide, will provide a unique method for structural control of a peptide helix through the use of external chirality. On the other hand, the NCDE has not been considered to be effective for the helicity control of peptides strongly favoring a one-handed screw sense. We here aim to promote the NCDE on peptide helicity using two types of nonapeptides: H-beta-Ala-Delta(Z)Phe-Aib-Delta(Z)Phe-X-(Delta(Z)Phe-Aib)(2)-OCH(3) [Delta(Z)Phe = alpha,beta-didehydrophenylalanine, Aib = alpha-aminoisobutyric acid], where X as the single chirality is L-leucine (1) or L-phenylalanine (2). NMR, IR, and CD spectroscopy as well as energy calculation revealed that both peptides alone form a right-handed 3(10)-helix. The original CD amplitudes or signs in chloroform, irrespective of a strong screw-sense preference in the central chirality, responded sensitively to external chiral information. Namely added Boc-L-amino acid stabilized the original right-handed helix, while the corresponding d-isomer destabilized it or transformed it into a left-handed helix. These peptides were also shown to bind more favorably to an L-isomer from the racemate. Although similar helicity control was observed for analogous nonapeptides bearing an N-terminal Aib residue (Inai, Y.; et al. Biomacromolecules 2003, 4, 122), the present findings demonstrate that the N-terminal replacement by the beta-Ala residue significantly improves the previous NCDE to achieve more effective control of helicity. Semiempirical molecular orbital calculations on complexation of peptide 2 with Boc-(L or D)-Pro-OH reasonably explained the unique conformational change induced by external chirality.

  • [Show abstract] [Hide abstract]
    ABSTRACT: By exploiting intramolecular interactions such as dipole repulsion, and by incorporating a terminal chiral controlling feature, the global conformation of a molecule may be governed. In such an environment, stereoselective reactions can occur at considerable distances from the source of stereochemical information, providing a simple method for information relay over scales of >1 nm (or about seven bond lengths). This tutorial review discusses the development of this idea, and describes examples which depend on relayed dipole repulsion and on the absolute control of helicity. Future prospects in the area employing control over extended helical foldamers are elaborated.
    Chemical Society Reviews 04/2009; 38(3):817-29. · 24.89 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Conformations of two pairs of dehydropeptides with the opposite configuration of the ΔPhe residue, Boc-Gly-Δ(Z)Phe-Gly-Phe-OMe (Z-OMe), Boc-Gly-Δ(E)Phe-Gly-Phe-OMe (E-OMe), Boc-Gly-Δ(Z)Phe-Gly-Phe-p-NA (Z-p-NA), and Boc-Gly-Δ(E)Phe-Gly-Phe-p-NA (E-p-NA) were compared on the basis of CD and NMR studies in MeOH, trifluoroethanol (TFE), MeCN, chloroform, and dimethylsulfoxide (DMSO). The CD results were used as the additional input data for the NMR-based determination of the detailed solution conformations of the peptides. It was found that E-OMe is unordered and Z-OMe, Z-p-NA, and E-p-NA adopt the β-turn conformation. There are two overlapping β-turns in each of those peptides: type II and type III' in Z-OMe and Z-p-NA, and two type III in E-p-NA. The ordered structure-inducing properties of Δ(Z)Phe and Δ(E)Phe in the peptides studied depend on the C-terminal blocking group. In methyl esters, the Δ(Z)Phe residue is a strong inducer of ordered conformations whereas the Δ(E)Phe one has no such properties. In p-nitroanilides, both isomers of ΔPhe cause the peptides to adopt ordered structures to a similar extent.
    Biopolymers 12/2010; 93(12):1055-64. · 2.88 Impact Factor
  • KOBUNSHI RONBUNSHU 01/2010; 67(3):214-223.