Ultraeffective Inhibition of Amyloid Fibril Assembly by Nanobody–Gold Nanoparticle Conjugates
发布时间：2023-07-20
点击次数：
- 发表刊物：
- BIOCONJUGATE CHEMISTRY
- 卷号：
- 30
- 期号：
- 1
- 页面范围：
- 29-33
- ISSN号：
- 1043-1802
- DOI码：
- 10.1021/acs.bioconjchem.8b00797
- 发表时间：
- 2018-12-08
- 影响因子：
- 4.349
- 摘要：
- Amyloid fibril assembly is associated with many human disorders, and to approach an inhibitor of amyloid formation that is effective at ultralow stoichiometric concentrations remains a big challenge. Taking fibril assembly of human islet amyloid polypeptide (IAPP) as a model system, we demonstrate here that conjugating a rationally designed sequence-specific nanobody inhibitor M1 with gold nanoparticles (AuNPs) can significantly enhance the inhibition potency of M1, leading to complete inhibition of IAPP amyloid fibrillation at very low M1:IAPP molar ratios. Thioflavin T kinetics fluorescence assays, dynamic light scattering measurements, far-UV circular dichroism, and transmission electron microscopy all indicate that M1-AuNP conjugates prevent IAPP fibrillation at M1:IAPP molar ratios of as low as 1:50, while free M1 is unable to prevent fibrillation at the same substoichiometric concentrations. This strategy represents a prototype of the facile development of a variety of highly potent amyloid inhibitors with enhanced therapeutic effects.