Structural studies by H-1 NMR of a prototypic alpha-helical peptide (LYQELQKLTQTLK) and homologs in trifluoroethanol/water and on sodium dodecyl sulfate micelles

The H-1 NMR-determined structure and dynamics of a synthetic, amphiphilic alpha-helical peptide, PM-1.0 (LYQELQKLTQTLK), and several homologs were compared in 50% trifluoroethanol-d(2) (TFE-d(2))/H2O and in sodium dodecyl-d(25) sulfate (SDS-d(25)) micelles. The peptides were designed to test the influence on secondary structure of placement of favored and disfavored residues relative to a ''longitudinal, hydrophobic strip-of-helix'' defined by the repeating leucines. PH-1.0 was highly ordered as an alpha-helix in 50% TFE-d(2)/H2O and in SDS-d(25) micelles. Homologs PH-1.1, in which L1 was replaced by T, and PH-1.4, in which L12 was replaced by T, were found to be partially helical in both media. Calculated structures in SDS-d(25) revealed that the helix of PH-1.1 was slightly disordered at the N-terminus, but that of PH-1.4 was completely disordered at the C-terminus. Examination of distributions of hydrophobic residues in protein structures revealed that, when lozenge = LIVFM and lozenge = nonLIVFM, the pattern lozenge lozenge lozenge lozenge lozenge is favored and lozenge lozenge lozenge lozenge lozenge is disfavored in alpha-helices, Several analogs of PH-1.0 incorporating these patterns were studied. Peptide PH-1.12 ((L) under bar YQE (L) under bar QK<(LL)under bar>QT (L) under bar K) retained alpha-helical structure in both 50% TFE-d(2)/H2O and in SDS-d(25) micelles. However, although PH-1.13 ((L) under bar YQE (L) under bar QK (L) under bar T (L) under bar T (L) under bar K) was fully helical in 50% TFE, it was helical only through residue 6 in SDS micelles. Two homologs containing an additional loop of the helix and repeats of favored (PH-5.0. NY (L) under bar QT<(LL)under bar>ET (L) under bar KT<(LL)under bar>QK) or suppressed LL patterns (PH-5.11, NY (L) under bar QT (L) under bar ELT (L) under bar K (L) under bar T (L) under bar QK) gave similar results, i.e. the latter peptide was helical only through residue 6 in SDS micelles. The degree of local order in these SDS micelle-adsorbed peptides correlates to placement of hydrophobic residues in motifs which are favored or disfavored in proteins in general and in alpha-helices specifically. (C) Munksgaard 1997.