CIRCULAR-DICHROISM OF MODEL PEPTIDES EMULATING THE AMPHIPATHIC ALPHA-HELICAL REGIONS OF INTERMEDIATE FILAMENTS

The a and d positions of the heptad repeats (abcdefg) found in the alp ha-helical sections of intermediate-filament proteins are hydrophobic, and the remaining locations are almost exclusively hydrophilic and of ten charged. Two synthetic peptides that maximize these features were designed, synthesized, and investigated by circular dichroism for alph a-helix formation in water and in 50% trifluoroethanol (TFE). A 14-res idue peptide, AcNLEELKKKLEELKGNH(2) (NLEKG14), had mean residue ellipt icities at 222 nm ([theta](222)) Of -18 400 +/- 1000 and -37 200 +/- 1 900 deg cm(2) dmol(-1), in water at 2 degrees C and in 50% TFE at 2 de grees C, respectively. A longer version of NLEKG14, AcNLEELKKKLEEL-KQQ LEELKKKLEELKQQNH(2) (NLEKQ29), had [theta](222) Of -43 000 +/- 2200 de g cm(2) dmol(-1) in water and in 50% TFE at 2 degrees C. Using -43 000 deg cm(2) dmol(-1) as [theta]222 for a 100% helix, NLEKG14 in 50% TFE at 25 degrees C was estimated to be 77% helix. This estimate was conf irmed by two-dimensional H-1 NMR studies of NLEKG14 in 50% TFE. Compar ison with the sequences and conformations found in IF proteins indicat es that the alpha-helical regions in the proteins may be exceptionally stable, but the high values for the ellipticity of alpha-helices now revealed allow for significant portions of the protein rod regions to be occupied by conformations other than alpha-helix.