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论文类型：期刊论文

发表刊物：Bioconjugate Chemistry

收录刊物：SCI

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：2019-01-02

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.

发布期刊链接：https://pubs.acs.org/doi/10.1021/acs.bioconjchem.8b00797