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Stereochemical specificity of Alzheimer's disease ?-peptide assembly

1999; Wiley; Volume: 49; Issue: 6 Linguagem: Inglês

10.1002/(sici)1097-0282(199905)49

1097-0282

William P. Esler, Evelyn R. Stimson, Jordan B. Fishman, Joseph R. Ghilardi, Harry V. Vinters, Patrick W. Mantyh, John E. Maggio,

Protein Structure and Dynamics

BiopolymersVolume 49, Issue 6 p. 505-514 Stereochemical specificity of Alzheimer's disease β-peptide assembly William P. Esler, William P. Esler Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115Search for more papers by this authorEvelyn R. Stimson, Evelyn R. Stimson Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115Search for more papers by this authorJordan B. Fishman, Jordan B. Fishman Quality Controlled Biochemicals, Hopkinton, MA 01748-2215Search for more papers by this authorJoseph R. Ghilardi, Joseph R. Ghilardi Molecular Neurobiology Laboratory (151), Veterans' Administration Medical Center and Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455Search for more papers by this authorHarry V. Vinters, Harry V. Vinters Department of Pathology and Laboratory Medicine and Brain Research Institute, University of California, Los Angeles Medical Center, Los Angeles CA 90095-1732Search for more papers by this authorPatrick W. Mantyh, Patrick W. Mantyh Molecular Neurobiology Laboratory (151), Veterans' Administration Medical Center and Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455Search for more papers by this authorJohn E. Maggio, Corresponding Author John E. Maggio Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115Department of Pharmacology and Cell Biophysics, Univesity of Cincinnati College of Medicine, Cincinnati OH 45267Search for more papers by this author William P. Esler, William P. Esler Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115Search for more papers by this authorEvelyn R. Stimson, Evelyn R. Stimson Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115Search for more papers by this authorJordan B. Fishman, Jordan B. Fishman Quality Controlled Biochemicals, Hopkinton, MA 01748-2215Search for more papers by this authorJoseph R. Ghilardi, Joseph R. Ghilardi Molecular Neurobiology Laboratory (151), Veterans' Administration Medical Center and Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455Search for more papers by this authorHarry V. Vinters, Harry V. Vinters Department of Pathology and Laboratory Medicine and Brain Research Institute, University of California, Los Angeles Medical Center, Los Angeles CA 90095-1732Search for more papers by this authorPatrick W. Mantyh, Patrick W. Mantyh Molecular Neurobiology Laboratory (151), Veterans' Administration Medical Center and Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455Search for more papers by this authorJohn E. Maggio, Corresponding Author John E. Maggio Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115Department of Pharmacology and Cell Biophysics, Univesity of Cincinnati College of Medicine, Cincinnati OH 45267Search for more papers by this author First published: 17 March 1999 https://doi.org/10.1002/(SICI)1097-0282(199905)49:6 3.0.CO;2-ICitations: 37AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The formation and growth of insoluble amyloid deposits composed primarily of the human β-amyloid peptide (Aβ) in brain is an essentially invariant feature of Alzheimer's disease (AD) and is widely believed to contribute to the progressive neurodegeneration of the disorder. To probe the specificity of amyloid formation and growth, we synthesized and examined the self-assembly of D- and L-stereoisomers of Aβ in vitro. While both enantiomers formed insoluble aggregates at similar rates with amyloid-like fibrillar morphology, deposition of soluble Aβ peptide onto preexisting Aβ aggregates was stereospecific. Although the L-peptide deposited readily onto immobilized L-Aβ aggregates with first-order kinetic dependence on soluble peptide concentration, essentially no association between the D-peptide and L-template was observed. Similarly, the D-peptide deposited with first-order kinetics onto a D-Aβ aggregate template but did not deposit onto a similar template composed of aggregates of the L-enantiomer. Furthermore, although the L-Aβ isomer deposited onto authentic AD amyloid in preparations of unfixed AD brain, no focal association between the D-peptide and brain amyloid was detected. These results establish that deposition of soluble Aβ onto preexisting amyloid template is stereospecific, likely involving direct docking interactions between peptide backbone and/or side chains rather than simple hydrophobic association. © 1999 John Wiley & Sons, Inc. Biopoly 49: 505–514, 1999 Citing Literature Volume49, Issue6May 1999Pages 505-514 RelatedInformation