Study of the non-covalent interaction between amyloid-beta-peptide and melatonin using electrospray ionization mass spectrometry.
Oxidative stress and unregulated immune response are believed to play a key role in the processes inherent to Alzheimer's disease (AD). The fact that free radicals can result in neurodegeneration suggests that actions against reactive oxygen species may be beneficial in treating and preventing AD. In the light of the suggested link between oxidative stress and AD, it is proposed that antioxidants and, even more, endogenous antioxidants may offer a therapeutic regime for protection against the risk of this disease. For this reason, the formation of non-covalent complexes between amyloid-beta-peptide (A beta) or its oxidized forms and melatonin was studied by quadrupole and Fourier transform ion cyclotron resonance electrospray ionization mass spectrometry. The stability of the non-covalent complex was examined under several experimental conditions, such as orifice voltage, pH, presence of organic modifier, concentration and time. Two different digestion protocols combined with mass spectrometric analysis of the resulting peptide fragments were employed in order to locate the binding site of melatonin in A beta.
Bazoti
Fotini N
FN
GAIA Research Center, The Goulandris Natural History Museum, 13 Levidou str., Kifissia 145 62, Greece.
Tsarbopoulos
Anthony
A
Markides
Karin E
KE
Bergquist
Jonas
J
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001665:Binding Sites; D002918:Chymotrypsin; D008550:Melatonin / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry*; D025941:Protein Interaction Mapping; D012697:Serine Endopeptidases; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013997:Time Factors; D014357:Trypsin
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D012697:Serine Endopeptidases; D002918:Chymotrypsin; C028344:glutamyl endopeptidase; D014357:Trypsin; D008550:Melatonin