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, amphiphi lic alpha-helical peptide, PM-1.0 (LYQELQKLTQTLK), and several homolog s were compared in 50% trifluoroethanol-d(2) (TFE-d(2))/H2O and in sod ium dodecyl-d(25) sulfate (SDS-d(25)) micelles. The peptides were desi gned to test the influence on secondary structure of placement of favo red 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) micelle s. Homologs PH-1.1, in which L1 was replaced by T, and PH-1.4, in whic h L12 was replaced by T, were found to be partially helical in both me dia. 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 loze nge = LIVFM and lozenge = nonLIVFM, the pattern lozenge lozenge lozeng e lozenge lozenge is favored and lozenge lozenge lozenge lozenge lozen ge is disfavored in alpha-helices, Several analogs of PH-1.0 incorpora ting 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-helic al structure in both 50% TFE-d(2)/H2O and in SDS-d(25) micelles. Howev er, 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 w as helical only through residue 6 in SDS micelles. Two homologs contai ning an additional loop of the helix and repeats of favored (PH-5.0. N Y (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 re sults, i.e. the latter peptide was helical only through residue 6 in S DS micelles. The degree of local order in these SDS micelle-adsorbed p eptides correlates to placement of hydrophobic residues in motifs whic h are favored or disfavored in proteins in general and in alpha-helice s specifically. (C) Munksgaard 1997.