Influence of methionine–ruthenium complex on the fibril formation of human islet amyloid polypeptide

  • Gehui Gong
  • Jufei Xu
  • Xiangyi Huang
  • Weihong DuEmail author
Original Paper


The abnormal aggregation and deposition of human islet amyloid polypeptide (hIAPP) are implicated in the pathogeny of type 2 diabetes mellitus (T2DM). Many aromatic ring-containing Ru complexes inhibit the aggregation of hIAPP. A new Ru complex Ru(bipy)(met)2·3H2O (1), where bipy is 2,2ʹ-bipyridine and met is methionine, was synthesized and employed to resist the fibril formation of hIAPP and to promote the biocompatibility of metal complexes. Two polypyridyl Ru complexes, namely [Ru(bipy)3]Cl2(2) and Ru(bipy)2Cl2(3), were used for comparison. Results reveal that the three Ru complexes can inhibit hIAPP aggregation and depolymerize mature hIAPP fibrils. Interaction studies show that Ru complexes bind to hIAPP through metal coordination, hydrophobic interaction, and other intermolecular forces. The binding of the three compounds is spontaneous and exothermic. The compounds also rescue peptide-induced cytotoxicity to some extent. Similar to 3, the novel methionine–Ru complex 1 exhibits an enhanced inhibitory effect and binding affinity to hIAPP possibly because of the smaller steric hindrance and more profitable molecular configuration of 1 than those of 2. The newly designed amino acid–Ru complex may provide new insights into the treatment of T2DM and related amyloidosis diseases.

Graphical abstract

Methionine–Ru complex effectively impedes the fibril formation of human islet amyloid polypeptide.


hIAPP Fibril formation Ruthenium complexes Inhibition 



We are grateful for the support of the National Natural Science Foundation of China (Nos. 21473251 & 21271185).

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest to declare.

Supplementary material

775_2019_1637_MOESM1_ESM.pdf (1.6 mb)
Supplementary material 1 (PDF 1625 kb)


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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • Gehui Gong
    • 1
  • Jufei Xu
    • 1
  • Xiangyi Huang
    • 1
  • Weihong Du
    • 1
    Email author
  1. 1.Department of ChemistryRenmin University of ChinaBeijingChina

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