Structural, kinetic and cytotoxicity aspects of 12-28 beta-amyloid protein fragment: a reappraisal.
A chemical, structural and biological study on the beta-amyloid peptide beta12-28 is reported which was carried out in order to assess the feasibility using this peptide fragment as a model of the natural beta-amyloid protein. The aggregation properties of beta12-28 have been investigated by pulse field-gradient NMR spectroscopy, Fourier transform infrared spectroscopy and transmission electron microscopy. The results obtained suggest that beta12-28 behaviour is comparable to that of the natural beta-amyloid protein although kinetically slower. Translational diffusion coefficients obtained by NMR on an aged beta12-28 solution suggest that the soluble peptide fraction is composed of oligomeric intermediates adopting an extended ellipsoidal assembly rather than a spherical one. The beta12-28 peptide proved to be cytotoxic in PC12 cell cultures as monitored by the MTT assay, although a lack of reproducibility was observed in the dose-response experiments.
Rabanal
Francesc
F
Departament de Química Orgànica, Universitat de Barcelona, Marti i Franques, 1-1 1, 08028 Barcelona, Spain.
Tusell
Josep M
JM
Sastre
Lluis
L
Quintero
M Rosa
MR
Cruz
Montse
M
Grillo
Dolors
D
Pons
Miquel
M
Albericio
Fernando
F
Serratosa
Joan
J
Giralt
Ernest
E
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D051381:Rats; D015203:Reproducibility of Results; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C092395:amyloid beta-protein (12-28)