title: Racemization of the amyloidal beta Asp1 residue blocks the acceleration of fibril formation caused by racemization of the Asp23 residue.
abstract: Amyloid beta proteins extracted from the amyloid cores of neuritic plaques are considerably racemized at their Asp residues. To assess the impact of D-Asp on amyloid beta(1-42) conformation and on initiation of amyloid fibril formation, we used wild-type amyloid beta(1-42) and analogs in which D-Asp was substituted for L-Asp at residues 1, 7, 23, and all combinations of these residues. Amyloid fibril formation was enhanced by D-Asp23; modulation of Asp chirality at N-terminal position 1 blocked this enhancement and modulation at position 7 augmented it. Knowledge of such chirality modifications may help to develop potent inhibitors of amyloid fibril formation.
authors.affiliation: Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. kumikato@musashino-u.ac.jp
authors.forename: Kumiko
authors.initials: K
authors.lastname: Sakai-Kato
authors.forename: Megumi
authors.initials: M
authors.lastname: Naito
authors.forename: Naoko
authors.initials: N
authors.lastname: Utsunomiya-Tate
mesh_terms: D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000648:ultrastructure*; D001224:Aspartic Acid / Q000737:chemistry*; D019281:Dimerization; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D001224:Aspartic Acid