Solution Structures of i to i + 3 Cyclized Model Peptides: Building Blocks Mimicking Specific Conformations
The structural features of model N α-acetyl carboxyl-amide cyclic tetrapeptides with the sequence Xxx-Pro-Gly-Zzz where Xxx = Lys, Orn, Dab, and Dpr; Zzz = Glu and Asp (Dab, α, γ-diaminobutyric acid; Dpr, α,β-diaminopropionic acid) were studied to examine the influence of side chain lactamization on...
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Veröffentlicht in: | Journal of the American Chemical Society 1996-07, Vol.118 (28), p.6531-6539 |
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Hauptverfasser: | , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
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Zusammenfassung: | The structural features of model N α-acetyl carboxyl-amide cyclic tetrapeptides with the sequence Xxx-Pro-Gly-Zzz where Xxx = Lys, Orn, Dab, and Dpr; Zzz = Glu and Asp (Dab, α, γ-diaminobutyric acid; Dpr, α,β-diaminopropionic acid) were studied to examine the influence of side chain lactamization on the stereochemical freedom of the backbone residues in i to i + 3 systems. Some of these cyclic peptides separate into distinct isomers at room temperature as evidenced by HPLC and NMR. Detailed analyses were carried out using 2D NMR and molecular modeling to unravel the structures of major conformers assumed by the cyclic peptides. Interproton distances obtained from ROESY spectra, amide proton temperature coefficients, backbone dihedral angles deduced from homonuclear coupling constants, and modeling studies (constrained annealing search, minimization, and dynamics simulations using the AMBER force field) suggest that in DMSO-d 6 solution these cyclic peptides adopt a variety of conformations that can be related to type II β-turns and γ-turns, but never to type I β-turns. The peptide backbone conformation, in this closely related series of cyclic peptides, is a function of the composition of the side chain but not the ring size. |
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ISSN: | 0002-7863 1520-5126 |
DOI: | 10.1021/ja954217i |