210345-74-7Relevant 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.
β2- And β3-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
Seebach, Dieter,Abele, Stefan,Gademann, Karl,Guichard, Gilles,Hintermann, Tobias,Jaun, Bernhard,Matthews, Jennifer L.,Schreiber, Juerg V.,Oberer, Lukas,Hommel, Ulrich,Widmer, Hans
, p. 932 - 982 (2007/10/03)
Enantiomerically pure β-amino-acid derivatives 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) have been prepared (compounds 8-17) and incorporated (by stepwise synthesis and fragment coupling, intermediates 24-34) into β-hexa-, β-hepta-, and β-dodecapeptides (1-17). The new and some of the previously prepared β-peptides (35-39) showed NH/ND exchange rates (in MeOH at room temperature) with τ1/2 values of up to 60 days, unrivalled by short chain α-peptides. All β-peptides 1-7 were designed to be able to attain the previously described 31-helical structure (Figs. 1 and 2). CD Measurements (Fig. 4), indicating a new secondary structure of certain β-peptides constructed of β2- and β3-amino acids, were confirmed by detailed NMR solution-structure analyses: a β2-heptapeptide (2c) and a β2,3-hexapeptide (7c) have the 31-helical structure (Figs. 6 and 7), while to a β2/β3-hexapeptide (4) with alternating substitution pattern H-(β2-Xaa-β3-Xaa)3-OH a novel, unusual helical structure (in (D5)pyridine, Fig. 8; and in CD3OH, Figs. 9 and 10) was assigned, with a central ten-membered and two terminal twelve-membered H-bonded rings, and with C=O and N-H bonds pointing alternatively up and down along the axis of the helix (Fig. 11). Thus, for the first time, two types of β-peptide turns have been identified in solution. Hydrophobic interactions of and hindrance to solvent accessibility by the aliphatic side chains are discussed as possible factors influencing the relative stability of the two types of helices.
