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, Aβ 25-35 and Aβ 12-28. Firstly, computational studies showed the limits of log D(7.4)oct 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 Aβ 25-35 and Aβ 12-28 in giving interactions with polar and apolar environments. CD studies were also performed to validate chromatographic experimental conditions. Results show that Aβ 12-28 has a larger skill in promoting hydrophobic and electrostatic interactions than Aβ 25-35. 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.
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
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Ermondi
Chemistry Department, Università degli Studi di Torino, Via Giuria 5, 10125 Torino, Italy.
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Catalano
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
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Vallaro
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
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Ermondi
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
M P Camacho
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Leal
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
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Rinaldi
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy.
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Visentin
Molecular Biotechnology and Health Sciences Department, Università degli Studi di Torino, via Quarello 15, 10135 Torino, Italy. Electronic address: giulia.caron@unito.it.
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Caron
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002845:Chromatography; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D055672:Static Electricity
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments
Amyloid peptide; Circular dichroism; Lipophilicity; Molecular dynamics