The anomalous infrared amide I intensity distribution in C-13 isotopicallylabeled peptide beta-sheets comes from extended, multiple-stranded structures. An ab initio study

Ab initio based calculations of force fields and atomic polar tensors are u sed to simulate amide I infrared absorption spectra for a series of isotopi cally substituted (Ac-A(12)-NH-CH3)(n) peptides clustered in an antiparalle l beta -sheet conformation having a varying number of strands, n = 2-5. The results demonstrate that the anomalous intensity previously reported for t he isotopically shifted amide 1 in C-13 labeled peptides is due to formatio n of multistranded beta -sheet structures in this conformation. Computation s show that the characteristic widely split amide 1 mode for beta -sheet po lypeptides as well as this anomalous intensity enhancement in isotopically substituted beta -sheet peptides grows with increasing sheet size. For shee ts of five strands, qualitative and near quantitative agreement with experi mental amide I intensity patterns is obtained for both labeled and unlabele d peptides. The strongest transitions primarily represent in-phase coupled modes of the C-13 labeled, next nearest neighbor amides on the inner strand s of the multistranded beta -sheet. Long-range transition dipole coupling i nteractions do not promote the C-13 amide I intensity enhancement. Understa nding of the IR intensity mechanisms with this level of detail for the isot opically labeled peptides permits design of site-specific probes of beta -s heet folding and unfolding dynamics.