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Structure and Conformation of β ‐Oligopeptide Derivatives with Simple Proteinogenic Side Chains: Circular Dichroism and Molecular Dynamics Investigations
Author(s) -
Seebach Dieter,
Schreiber Jürg V.,
Abele Stefan,
Daura Xavier,
van Gunsteren Wilfred F.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(20000119)83:1<34::aid-hlca34>3.0.co;2-b
Subject(s) - chemistry , circular dichroism , oligopeptide , stereochemistry , peptide , helix (gastropod) , crystallography , molecular dynamics , ring (chemistry) , cyclic peptide , structural motif , proton nmr , cotton effect , computational chemistry , organic chemistry , ecology , biochemistry , snail , biology
A careful CD analysis ( Figs. 1 – 3 and 5 ; MeOH or H 2 O 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 3 14 ‐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 3 14 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 β 2,3 ‐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.