Solution NMR structure of a model class A (apolipoprotein) amphipathic α helical peptide☆

Abstract

To better understand the structural determinants of the physical-chemical and the biological properties of Ac-18A-NH 2 (acetyl-AspTrpLeuLysAlaPheTyrAspLysValAlaGluLysLeuLysGluAlaPhe-amide), we have determined its structure in 50% (v/v) trifluroethanol (TFE-d 3)/water mixture (5 mM potassium phosphate, pH 5.5, 310K) using two-dimensional proton NMR spectroscopy. Stereospecific assignments have been made for C βH protons (all the residues except Ala and Val) and γCH 3 (Val) groups. Nuclear Overhauser effects are observed between the nonpolar side chains spaced at (i) and (i + 4) position in the primary sequence, e.g., Trp2 and Phe6, and Phe6 and Val10. This suggests that in addition to N-terminal acetyl and C-terminal amide groups, the amphipathic α helical structure of Ac-18A-NH 2 is further stabilized by interactions between the hydrophobic residues on the nonpolar face of the helix.