Stabilization of secondary structure of Alzheimer beta-protein by aluminum(III) ions and D-Asp substitutions.
The CD spectra of the D-Asp substituted analogs of amyloid peptides, beta 6-25 and beta 1-40, showed a distinct blue-shift on Al3+ complexation. The influence of Al3+ coordination was most significant on the triply substituted beta 1-40 (D-Asp 1,7,23). This analog showed a reduction of the minima near 210nm and a simultaneous increase in the maxima near 200nm as compared to the native L-Asp beta 1-40. These observations suggest that Al3+ interaction with D-Asp induces the peptide backbone to increase its antiparallel beta-sheet character. D-Asp substitution and chelation by Al3+ lead to increased stability of higher molecular weight species of beta 1-40, and thereby could increase the toxicity of the Alzheimer amyloid protein.
Vyas
S B
SB
Department of Chemistry and Biochemistry, University of Alaska Fairbanks, Fairbanks 99775.
Duffy
L K
LK
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000187:drug effects; D001224:Aspartic Acid; D002942:Circular Dichroism; D003300:Copper / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry; D017433:Protein Structure, Secondary / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C091513:amyloid beta-protein (6-25); D001224:Aspartic Acid; D003300:Copper