Change and stabilization of the amyloid-beta(1-40) secondary structure by fluorocompounds.
The misfolding of the amyloid peptide, which is the result of a well-known alpha-to-beta transition, causes neurodegenerative disorder. Fluorinated alcohols have been described in the literature as potent solvents which can refold the beta-conformation. The present studies demonstrate the effectiveness of differently fluorinated alcohols for the beta-to-alpha refolding process on fibrillar aggregated amyloid beta(1-40). The regenerated helical structure is shown to be maintained in the absence of the fluoroalcohols, a behaviour which was found to contrast with immunoglobulin. We interpret this difference on the basis of the hydrophilic/hydrophobic domains in the amyloid sequence and present some speculations regarding the free-energy levels of the folded states of both proteins. The effect of the -CF(3) group on the observed conformational changes is interpreted as a result of alterations of the hydration shell of the peptides. Moreover, based on the results achieved with fluoroalcohols, we have used novel fluorinated amphiphiles possessing blood-compatibility properties and studied their effect on amyloid beta(1-40). First results point in the direction of a beta-to-alpha transition. Therefore, the use of fluorine groups in the development of new drugs is considered a new possibility requiring further investigation for the prevention of amyloidosis.
Vieira
Euridice P
EP
Max-Planck-Institute for Colloids and Interfaces, Campus Golm, D-14476, Potsdam, Germany.
Hermel
Horst
H
Möhwald
Helmuth
H
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000686:Amyloidosis / Q000517:prevention & control; D002942:Circular Dichroism; D015195:Drug Design; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D014270:Trifluoroethanol / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated
D016229:Amyloid beta-Peptides; D000431:Ethanol; D010446:Peptide Fragments; D020005:Propanols; D012996:Solutions; D014270:Trifluoroethanol; C078592:amyloid beta-protein (1-40); C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated