title: Structural studies by 1H NMR of a prototypic alpha-helical peptide (LYQELQKLTQTLK) and homologs in trifluoroethanol/water and on sodium dodecyl sulfate micelles.
abstract: The 1H NMR-determined structure and dynamics of a synthetic, amphiphilic alpha-helical peptide, PH-1.0 (LYQELQKLTQTLK), and several homologs were compared in 50% trifluoroethanol-d2 (TFE-d2)/H20 and in sodium dodecyl-d25 sulfate (SDS-d25) 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-d2/H20 and in SDS-d25 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-d25 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 [symbol: see text] = LIVFM and [symbol: see text] = nonLIVFM, the pattern [symbol: see text] is favored and [symbol: see text] is disfavored in alpha-helices. Several analogs of PH-1.0 incorporating these patterns were studied. Peptide PH-1.12 (LYQELQKLLQTLK) retained alpha-helical structure in both 50% TFE-d2/H20 and in SDS-d25 micelles. However, although PH-1.13 (LYQELQKLTLTLK) 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, NYLQTLLETLKTLLQK) or suppressed LL patterns (PH-5.11, NYLQTLETLKLTQK) 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.
authors.affiliation: Department of Pharmacology, University of Massachusetts Medical Center, Worcester, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Young
authors.forename: F
authors.initials: F
authors.lastname: Marí
authors.forename: M
authors.initials: M
authors.lastname: Xu
authors.forename: R E
authors.initials: RE
authors.lastname: Humphreys
authors.forename: N M
authors.initials: NM
authors.lastname: Clemente
authors.forename: J M
authors.initials: JM
authors.lastname: Stattel
authors.forename: D J
authors.initials: DJ
authors.lastname: Nelson
authors.forename: J
authors.initials: J
authors.lastname: Gambino
authors.forename: G E
authors.initials: GE
authors.lastname: Wright
mesh_terms: D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate; D012997:Solvents; D014270:Trifluoroethanol
chemical_list: D008823:Micelles; D009842:Oligopeptides; D012997:Solvents; D012967:Sodium Dodecyl Sulfate; D014270:Trifluoroethanol