VCD Studies of Peptide Models

A number of studies on polypeptides and oligopeptides have established the regularities of VCD spectra for amide vibrational modes (5-8). The amide I band (amide I' in D2O), mainly C=O stretch at ~1650 cm-1, is the most characteristic and easiest to study with VCD. The amide II (N-H deformation and C-N stretch) VCD seems less sensitive to variation in secondary structure (9), and the amide III (also N-H deformation and C-N stretch) is quite weak and mixed with non-amide modes(10). Some model peptide results are shown in Figure1 for alpha-helix, beta-sheet and random coils. (Isolated beta-sheets are difficult to measure under these conditions due to solubility and aggregation problems.) The alpha-helical result is maintained over a range of solvents and peptide lengths and compositions. The primary variation in the alpha-helical band shape is due to N-H deuteration, which causes the amide I' to have three features (-+-) rather than just the positive couplet pattern seen for protonated peptides and shifts the amide II down from ~1550 cm-1 to ~1450 cm-1 with loss of intensity. These studies have demonstrated that VCD of these amide modes exhibits a remarkable independence of the type of side chains on the peptide and a resolution of aromatic contributions in contrast to ECD (5). The beta-sheet VCD is less universal, being clearest (two weak negative bands at ~1615 and ~1685 cm-1) for the amide I' transitions of aggregated anti parallel structures in D2O solution (1,6). The 'random-coil' form in m any polypeptidesand proteins gives rise to a large negative couplet (5-7). Such a pattern implies that, in these 'random-coils', substantial local ordering exists that is similar in nature to that of left-handed helical poly-L-proline II, as has been supported by oligomer studies (7). Additionally, less common structuressuch as the 310 helix give distinct band shapes, particularly when several transitions are studied (8). Figure This experience with peptide VCD underpins development of a qualitative understanding of the VCD of proteins (1).

We have recently demonstrated that the characteristic VCD band shapes arise in large part from just the near-neighbor interactions in an oligopeptide by carrying out ab initio level magnetic field perturbation calculations of peptide VCDspectra (11). Calculations for just a dipeptide constrained to f,y angles characteristic of the secondary structures of interest yielded band shapes and relative intensities in very good agreement with the experimental results for polymers. These support our empirical observations, based on oligomer studies, that VCD for peptides has a relatively shorter range length dependence than does ECD.

--Research Topics--MVCD--Biopolymers--Instrumentation--Small Molecules--Other Interests--Keiderling Home--