Integrated Computational Approach to the Electron Paramagnetic Resonance Characterization of Rigid 3(10)-Helical Peptides with TOAC Nitroxide Spin Labels

We address the interpretation, via an integrated computational approach, of the experimental continuous-wave electron paramagnetic resonance (cw-EPR) spectra. of a complete set of conformationally highly restricted, stable 3(10)-helical peptides from hexa-to nonamers, each bis-labeled with nitroxide radical-containing TOAC (4-amino-l-oxyl-2,2,6,6-tetramethylpi peridine-4-carboxylic acid) residues. The usefulness of TOAC for this type Of analysis has been shown already to be due to its cyclic piperidine side chain, which is rigidly connected to the peptide backbone alpha-carbon. The TOAC alpha-ta amino acids are separated by two, three, four, and five intervening residues. This set of compounds has allowed us to modulate both the radical radical distance and the relative orientation parameters, To further validate our conclusion, a comparative analysis has been carried out on three singly TOAC-labeled peptides of similar Main-chain length