Tyrosine carbon dots inhibit fibrillation and toxicity of the human islet amyloid polypeptide

Daniel Nir Bloch; Shani Ben Zichri; Sofiya Kolusheva; Raz Jelinek

doi:10.1039/d0na00870b

Tyrosine carbon dots inhibit fibrillation and toxicity of the human islet amyloid polypeptide

Nanoscale Adv. 2020 Nov 10;2(12):5866-5873. doi: 10.1039/d0na00870b. eCollection 2020 Dec 15.

Authors

Daniel Nir Bloch¹, Shani Ben Zichri¹, Sofiya Kolusheva², Raz Jelinek^{1

2}

Affiliations

¹ Department of Chemistry, Ben Gurion University of the Negev Beer Sheva 84105 Israel razj@bgu.ac.il.
² Ilse Katz Institute for Nano-Science and Technology (IKI), Ben Gurion University of the Negev Beer Sheva 84105 Israel.

Abstract

Misfolding and aggregation of the human islet amyloid polypeptide (hIAPP) are believed to play key roles in the pathophysiology of type-II diabetes. Here, we demonstrate that carbon dots (C-dots) prepared from the amino acid tyrosine inhibit fibrillation of hIAPP, reduce hIAPP-induced cell toxicity and block membrane disruption by the peptide. The pronounced inhibitory effect is traced to the display of ubiquitous aromatic residues upon the C-dots' surface, mimicking the anti-fibril and anti-toxic activity of natural polyphenolic compounds. Notably, spectroscopy and thermodynamics analysis demonstrated different hIAPP interactions and fibril inhibition effects induced by tyrosine-C-dots displaying phenolic residues and C-dots prepared from phenylalanine which exhibited phenyl units on their surface, underscoring the significance of hydrogen bonding mediated by the phenolic hydroxide moieties for the fibril modulation activity. The presented experiments attest to the potential of tyrosine-C-dots as a therapeutic vehicle for protein misfolding diseases, interfering in both π-π interactions as well as hydrogen bonding involving aromatic residues of amyloidogenic peptides.