266318-86-9Relevant academic research and scientific papers
Structure and conformation of β-oligopeptide derivatives with simple proteinogenic side chains: Circular dichroism and molecular dynamics investigations
Seebach, Dieter,Schreiber, Juerg V.,Abele, Stefan,Daura, Xavier,Van Gunsteren, Wilfred F.
, p. 34 - 57 (2007/10/03)
A careful CD analysis (Figs. 1-3 and 5; MeOH or H2O solutions) of β- oligopeptides (1- 6, B, C) containing four to seven β-amino acids reveals that seemingly small structural changes cause a switch from the CD pattern (maxima of opposite sign near 215 and 200 nm) associated with a 314-helical structure to the CD pattern (single Cotton effect at ca. 205 nm) considered characteristic of a so-called 12/10-helical structure, but also exhibited by a β-peptide adopting a hair-pin conformation with a ten-membered H-bonded ring as the turn motif. Comparison of these CD spectra with those of the trans-2-aminocyclohexanecarboxamide oligomers, which give rise to the long- wavelength Cotton effect only, suggests that the H-bonded 14-, 12-, and 10- membered ring conformations of the β-peptides, and not just the entire helix structures, might actually generate the Cotton effects. This interpretation would be compatible with our previous NMR structure determinations of β- peptides and with previously reported temperature dependences of CD and NMR spectra of β-peptides. To further substantiate this suggestion, we have performed a statistical analysis of the β-peptidic conformations generated by molecular-dynamics calculations (GROMOS96) for a β-hexapeptide (C; the 12/10 helix) and a β-heptapeptide (6; the 314 helix) in MeOH (Figs. 6-9). Up to 400,000 conformations at 0.5-ps intervals were analyzed from up to 200- ns simulations (at 298 to 360 K). The analysis reveals the co-existence of the various H-bonded rings. Remarkably, the central section of the β-peptide 6 (containing a β2.3-amino-acid residue of like-configuration!) adopts a ten-membered-ring conformation for ca. 5% of the simulation time, while the central section of the β-peptide C adopts a 14-membered-ring conformation for ca. 3% of the time, according to this computational analysis. Further experimental and theoretical work will be necessary to find out to which extent the components (H-bonded rings) and the entire helical secondary structures of β-peptides contribute to the observed Cotton effects.
