Arrest of beta-amyloid fibril formation by a pentapeptide ligand
Arrest of beta-amyloid fibril formation by a pentapeptide ligand
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DOI：
10.1074/jbc.271.15.8545
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发表时间：
1996-04-12
影响因子：
4.8
通讯作者：
Nordstedt, C
中科院分区：
文献类型：
--
作者：
Tjernberg, LO;Naslund, J;Nordstedt, C
Polymerization of amyloid beta-peptide (A beta) into amyloid fibrils is a critical step in the pathogenesis of Alzheimer's disease, Here, we show that peptides incorporating a short A beta fragment (KLVFF; A beta(16-20)) can bind full-length A beta and prevent its assembly into amyloid fibrils, Through alanine substitution, it was demonstrated that amino acids Lys(16), Leu(17) and Phe(20) are critical for binding to A beta and inhibition of A beta fibril formation, A mutant A beta molecule, in which these residues had been substituted, had a markedly reduced capability of forming amyloid fibrils. The present data suggest that residues A beta(16-20) serve as a binding sequence during A beta polymerization and fibril formation, Moreover, the present KLVFF peptide may serve as a lead compound for the development of peptide and nonpeptide agents aimed at inhibiting A beta amyloidogenesis in vivo.
