Indexed by:Journal paper

Journal:Bioconjugate Chemistry

Included Journals:SCI

Volume:30

Issue:1

Page Number:29-33

ISSN No.:1043-1802

DOI number:10.1021/acs.bioconjchem.8b00797

Date of Publication:2019-01-02

Impact Factor:4.349

Abstract: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.

Links to published journals:https://pubs.acs.org/doi/10.1021/acs.bioconjchem.8b00797