Lipophilicity of amyloid β-peptide 12-28 and 25-35 to unravel their ability to promote hydrophobic and electrostatic interactions

The growing interest for peptide therapeutics calls for new strategies to determine the physico-chemical properties responsible for the interactions of peptides with the environment. This study reports about the lipophilicity of two fragments of the amyloid β-peptide, Aβ25-35 and Aβ12-28⋅ Firstly, computational studies showed the limits of log D7.4oct in describing the lipophilicity of medium-sized peptides. Chromatographic lipophilicity indexes (expressed as log k', the logarithm of the retention factor) were then measured in three different systems to highlight the different skills of Aβ25-35 and Aβ12-28 in giving interactions with polar and apolar environments. CD studies were also performed to validate chromatographic experimental conditions. Results show that Aβ12-28 has a larger skill in promoting hydrophobic and electrostatic interactions than Aβ25-35. This finding proposes a strategy to determine the lipophilicity of peptides for drug discovery purposes but also gives insights in unraveling the debate about the aminoacidic region of Aβ responsible for its neurotoxicity.