13C isotope labeling of hydrophobic peptides.: Origin of the anomalous intensity distribution in the infrared amide I spectral region of β-sheet structures

A series of isotopically substituted derivatives of the hydrophobic peptide K-2(LA)(6) including K(2)LA*(LA)(5), K2L*A*(LA)(5), and K-2 LA*LA*(LA)(4) (where the asterisk represents a residue with C-13 substitution in the peptide bond C=O) has been synthesized. The peptides adopt antiparallel beta-sheet conformations as revealed by solution CD and IR measurements. The amide I region of the IR spectrum is substantially altered by the isotopic labeling. Peaks of anomalously large intensity are observed on the low frequency (similar to 1610 cm(-1)) side of the major conformation marker at 1625-1630 cm(-1) present in the unlabeled isotopomer. The spectral changes cannot be described by the appearance of a pure mode based on the substitution of an oscillator of increased mass within the sequence. A semiempirical model incorporating transition dipole coupling and through-bond interactions within the context of the Wilson GF matrix method produces excellent agreement between calculated and observed amide I spectra with a single set of four parameters (through II-bond interaction force constant, through valence bond interaction force constant, transition dipole magnitude, and physical size) for four amide I beta-sheet contours. In addition, the model reproduces the amide I contour for an isotopically labeled derivative of the alpha-helical peptide K-2(LA)(10). The excellent agreement between calculated and experimental spectra suggests that the model accounts for the most important interactions between peptide groups with beta-sheet or alpha-helical structures.