Membrane Structure of Substance P. III. Secondary Structure of Substance P in 2,2,2‐Trifluoroethanol, Methanol, and on Flat Lipid Membranes Studied by Infrared Spectroscopy

Abstract

IR data of the neuropeptide substance P (1) and its synthetic segments des-(Arg'-Gin')-substance P (6), des-(Arg'-Pro4)-substance P (4), des-(Arg'-Lys3)-substance P (3), and des-Arg'-substance P (2) indicate predominant p-structures in the solid state and a-helical structures in CF,CH20H (amide I band shape analysis). In MeOH, the spectra of 1 suggest a partly helical structure. On membranes prepared from 1-palmitoyl-2-oleoyl-snglycero-3-phosphocholine, a C-terminal a-helix consisting of 8 or 9 peptide bonds appears to be induced (IR attenuated total reflection studies). Its perpendicular orientation on the membrane is suggested by the dichroic ratios of the amide-1 and -11 bands. This study is consistent with our CD experiments and lends support to the membrane structure of 1 predicted from the estimated amphiphilic moment, hydrophobic-association constant, and helix length.

The study of the conformation and interaction of two tachykinin peptides in membrane mimicking systems by NMR spectroscopy and pulsed field gradient diffusion

“…12 attributed this large upfield shift in ␦(NH) in Gly 9 to a general feature for glycine in peptides with the sequence Tyr/Phe-X-Gly observed by Kemmink et al 53 However, Chassaing et al 50 suggested that folding at the C-terminus (Gly-Leu-Met) of SP in solution results in the large chemical shift differences of Gly 9 12 for SP under similar conditions than to that for SP in 15 mM SDS reported by Young et al 13 The difference from the latter can either be due to the secondary structure, to the binding pattern, or both. The use of a lower micelle-to-peptide molar ratio (12.5:1), especially with the micelle concentration close to the cmc for SDS, and a lower pH value by Young et al 13 may account for this difference.…”

“…This may be a result of a less definite conformation for this peptide in SDS than in DPC. The NOE-derived distance restrained molecular modeling shows an approximate 3 10 -helical conformation over the midregion Pro 4 -Gly 9 . The dihedral angles and of this region range from Ϫ47°to Ϫ89°, and from 2°to Ϫ38°, respectively.…”

“…8 Schwyzer further proposed that nine C-terminal amino acid residues are inserted into the membrane as an ␣-helix perpendicular to an anionic bilayer surface. 7,9 Recently, a study dealing with the orientation and dynamics of SP in micelles was reported.…”

“…For [Tyr 0 ]NKA/SDS, 21 of 50 resulting structures had a global fold in the region from Thr 3 to Leu 9 that had RMSD of less than 0.55 Å and had no distance violations greater than 0.25 Å. The average energy of these structures was 160 kcal mol…”

Conformation Changes, Complexation, and Phase Transition in Matrix-Assisted Laser Desorption

“…[11][12][13][14][15][16] Different studies have shown that SP has no preferred conformation in aqueous solutions. 11,12,15 A mixed R-helix/folded structure in methanol has been proposed with five hydrogen bonds determining the conformation of the molecule.…”