Basic amphipathic model peptides: Structural investigations in solution, studied by circular dichroism, fluorescence, analytical ultracentrifugation and molecular modelling

Abstract

A twenty amino acid residue long amphipathic peptide made of ten leucine and ten lysine residues and four derivatives, in which a tryptophan, as a fluorescent probe, is substituted for a leucine, are studied. The peptides in water are mainly in an unordered conformation (~90%), and undergo a two state reversible transition upon heating, leading to a partially helical conformation (cold denaturation). Time resolved fluorescence results show that fluorescence decay for the four Trp containing peptides is best described by triple fluorescence decay kinetics. In TFE/water mixture, peptides adopt a single α-helix conformation but the Leu-Trp9 substitution leads to an effective helix destabilizing effect. In salted media, the peptides are fully helical and present a great tendency to self associate by bringing the hydrophobic faces of helices into close contact. This proceeds in non-cooperative multisteps leading to the formation of α helix aggregates with various degrees of complexation. Using modelling, the relative hydrophobic surface areas accessible to water molecules in n-mer structures are calculated and discussed.