Design strategies for anti-amyloid agents
Design strategies for anti-amyloid agents
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DOI：
10.1016/s0959-440x(03)00100-3
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发表时间：
2003-08-01
影响因子：
6.8
通讯作者：
Doig, AJ
中科院分区：
文献类型：
--
作者：
Mason, JM;Kokkoni, N;Doig, AJ
许多疾病都与一种称为淀粉样变性的常见致病过程有关，其中蛋白质或肽在大脑或身体中聚集在一起，形成有毒的可溶性低聚物和/或不溶性纤维。因此，开发用于这些疾病的疗法的有吸引力的策略是抑制或逆转蛋白质/肽聚集。已经发现各种各样的小有机配体作为聚集抑制剂。或者，野生型肽可以衍生化，使得其仍然结合淀粉样蛋白靶标，但防止进一步聚集。这可以通过将大体积基团或带电荷的氨基酸添加到肽的任一末端，或通过掺入脯氨酸残基或N-甲基化酰胺基团来实现。
Numerous diseases have been linked to a common pathogenic process called amyloidosis, whereby proteins or peptides clump together in the brain or body to form toxic soluble oligomers and/or insoluble fibres. An attractive strategy to develop therapies for these diseases is therefore to inhibit or reverse protein/peptide aggregation. A diverse range of small organic ligands have been found to act as aggregation inhibitors. Alternatively, the wild-type peptide can be derivatised so that it still binds to the amyloid target, but prevents further aggregation. This can be achieved by adding a bulky group or charged amino acid to either end of the peptide, or by incorporating proline residues or N-methylated amide groups.