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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
  • 24 Downloads

Abstract

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.

Keywords

hIAPP Fibril formation Ruthenium complexes Inhibition 

Notes

Acknowledgements

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)

References

  1. 1.
    Chiti F, Dobson CM (2006) Annu Rev Biochem 75:333–366CrossRefGoogle Scholar
  2. 2.
    Hu R, Zhang M, Chen H, Jiang B, Zheng J (2015) ACS Chem Neurosci 6:1759–1768CrossRefGoogle Scholar
  3. 3.
    Chitnis AS, Ganz ML, Benjamin N, Langer J, Hammer M (2014) Adv Ther 31:986–999CrossRefGoogle Scholar
  4. 4.
    Cameron FJ, Wherrett DK (2015) Lancet 385:2096–2106CrossRefGoogle Scholar
  5. 5.
    Clark A, Cooper GJ, Lewis CE, Morris JF, Willis AC, Reid KB, Turner RC (1987) Lancet 2:231–234CrossRefGoogle Scholar
  6. 6.
    Goldsbury C, Struct J (2000) Biol 130:352–362Google Scholar
  7. 7.
    Konarkowska B, Aitken JF, Kistler J, Zhang S, Cooper GJ (2006) FEBS J 273:3614–3624CrossRefGoogle Scholar
  8. 8.
    Höppener JW, Ahrén B, Lips CJ (2000) New Engl J Med 343:411–419CrossRefGoogle Scholar
  9. 9.
    Fang X, Yousaf M, Huang Q, Yang Y, Wang C (2018) Sci Rep 8:4463CrossRefGoogle Scholar
  10. 10.
    Mukherjee A, Morales-Scheihing D, Salvadores N, Gonzalez IC, Taylor-Presse K, Mendez N, Shahnawaz M, Gaber AO, Sabek OM, Fraga DW, Soto C (2017) J Exp Med 9:2591–2610CrossRefGoogle Scholar
  11. 11.
    Porat Y, Kolusheva S, Jelinek R, Gazit E (2003) Biochemistry 42:10971–11097CrossRefGoogle Scholar
  12. 12.
    Krotee P, Rodriguez JA, Sawaya MR, Cascio D, Reyes FE, Shi D, Hattne J, Nannenga BL, Oskarsson ME, Philipp S, Griner S, Jiang L, Glabe CG, Westermark GT, Gonen T, Eisenberg DS (2017) eLife 6:e19273CrossRefGoogle Scholar
  13. 13.
    Mukherjee S, Dey SD (2013) Inorg Chem 52:5226–5235CrossRefGoogle Scholar
  14. 14.
    Zhao Z, Li S, Liu G, Yan F, Ma X, Huang Z, Tian H (2012) PLoS One 7:e41641CrossRefGoogle Scholar
  15. 15.
    Seal M, Dey SD (2018) Inorg Chem 57:129–138CrossRefGoogle Scholar
  16. 16.
    Man B, Chan H, Leung C, Chan D, Bai L, Jiang Z, Li H, Ma D (2011) Chem Sci 2:917–921CrossRefGoogle Scholar
  17. 17.
    Sengupta K, Chatterjee S, Debajyoti Pramanik D, Dey SD, Dey A (2014) Dalton Trans 43:13377–13383CrossRefGoogle Scholar
  18. 18.
    Hu R, Zhang M, Chen H, Jiang B, Zheng J (2015) ACS Chem Neurosci 6:1759–1768CrossRefGoogle Scholar
  19. 19.
    Ma G, Huang F, Pu X, Jia L, Jiang T, Li L, Liu YZ (2011) Chem Eur J 17:11657–11666CrossRefGoogle Scholar
  20. 20.
    Kenche VB, Zawisza I, Masters CL, Bal W, Barnham KJ, Drew SC (2013) Inorg Chem 52:4303–4318CrossRefGoogle Scholar
  21. 21.
    Brender JR, Hartman K, Nanga RPR, Popovych N, de la Salud Bea R, Vivekanandan S, Ramamoorthy A (2010) J Am Chem Soc 132:8973–8983CrossRefGoogle Scholar
  22. 22.
    Andreadou E, Mitrakou A, Constantinides VC, Triantafyllou N (2012) J Diabetes Res Clin Metab 1:1–6CrossRefGoogle Scholar
  23. 23.
    Ward B, Walker K, Exley C (2008) J Inorg Biochem 102:371–375CrossRefGoogle Scholar
  24. 24.
    Rivillas-Acevedo L, Sanchez-Lopez C, Amero C, Quintanar L (2015) Inorg Chem 54:3788–3796CrossRefGoogle Scholar
  25. 25.
    Brender JR, Krishnamoorthy J, Messina JML, Deb A, Vivekanandan S, La Rosa C, Penner-Hahn JE, Ramamoorthy A (2013) Chem Commun 49:3339–3341CrossRefGoogle Scholar
  26. 26.
    Wang W, Zhao C, Zhu D, Gong G, Du W (2017) J Inorg Biochem 171:1–9CrossRefGoogle Scholar
  27. 27.
    Xu J, Gong G, Huang X, Du W (2018) J Inorg Biochem 186:60–69CrossRefGoogle Scholar
  28. 28.
    He L, Wang X, Zhao C, Wang H, Du W (2013) Metallomics 5:1599–16035CrossRefGoogle Scholar
  29. 29.
    Ma L, Fu Y, Yu L, Li X, Zheng W, Chen T (2015) RSC Adv 5:17405–17412CrossRefGoogle Scholar
  30. 30.
    Zhu D, Gong G, Wang W, Du W (2017) J Inorg Biochem 170:109–116CrossRefGoogle Scholar
  31. 31.
    Mamdouh S, Mohamed F, Ahmed M, Ghada M (2008) Spectrochim Acta A 69:230–238CrossRefGoogle Scholar
  32. 32.
    Nakabayashi Y, Watanabe Y, Nakao T, Yamauchi O (2004) Inorg Chim Acta 357:2553–2560CrossRefGoogle Scholar
  33. 33.
    Porto HKP, Vilanova-Costa CAST, Mello FMS, Costa WL, Lima AP, Pereira FC, Almeida MAP, Graminha AE, Batista AA, Silveira-Lacerda EP (2015) Transit Met Chem 401–410Google Scholar
  34. 34.
    Almeida MAP, Nascimento FB, Graminha AE, Ferreira AG, Ellena J, Mello FMS, Lima AP, Silveira-Lacerda EP, Batista AA (2014) Polyhedron 81:735–742CrossRefGoogle Scholar
  35. 35.
    Ma B, Qian H, Feng Y, Huang W (2016) Polyhedron 104:37–45CrossRefGoogle Scholar
  36. 36.
    Aïthaddou H, Bejan E, Daran JC (1999) J Chem Soc Dalton Trans 17:3095–3101CrossRefGoogle Scholar
  37. 37.
    Liao W, Zhang J, Hou Y (2016) Inorg Chem Commun 73:80–89CrossRefGoogle Scholar
  38. 38.
    Erkan Kariper S, Sayin K, Karakaş D (2017) J Mol Struc 1149:473–486CrossRefGoogle Scholar
  39. 39.
    Palmer RA, Piper TS (1966) Inorg Chem 5:864–878CrossRefGoogle Scholar
  40. 40.
    Sullivan B, Salmon D, Meyer T (1978) Inorg Chem 17:3334–3341CrossRefGoogle Scholar
  41. 41.
    He L, Wang X, Zhao C, Zhu D, Du W (2014) Metallomics 6:1087–1096CrossRefGoogle Scholar
  42. 42.
    Anderson CM, Taylor IR, Tibbetts MF, Philpott J, Hu YF, Tanski JM (2012) Inorg Chem 51:12917–12924CrossRefGoogle Scholar
  43. 43.
    Turoverov KK, Kuznetsova IM, Maskevich AA, Stepuro VI, Kuzmitsky VA, Uversky VN (2007) Int Conf Lasers Appl Technol 6733:R7331Google Scholar
  44. 44.
    Abedini A, Raleigh DP (2005) Biochemistry 44:16284–16291CrossRefGoogle Scholar
  45. 45.
    Marek PJ, Patsalo V, Green DF, Raleigh DP (2012) Biochemistry 51:8478–8490CrossRefGoogle Scholar
  46. 46.
    Tu L, Raleigh DP (2013) Biochemistry 52:333–342CrossRefGoogle Scholar
  47. 47.
    Zhu D, Zhao C, Wang X, Wang W, Wang B, Du W (2016) RSC Adv 6:16055–16065CrossRefGoogle Scholar
  48. 48.
    Cui F, Fan J, Li J, Hu Z (2004) Bioorg Med Chem 12:151–157CrossRefGoogle Scholar
  49. 49.
    Thompsett AR, Abdelraheim SR, Daniels M, Brown DR (2005) J Biol Chem 280:42750–42758CrossRefGoogle Scholar
  50. 50.
    Hebda JA, Saraogi I, Magzoub M, Hamilton AD, Miranker AD (2009) Chem Biol 16:943–950CrossRefGoogle Scholar
  51. 51.
    Guilloreau L, Damian L, Coppel Y, Mazarguil H, Winterhalter M (2006) J Biol Inorg Chem 11:1024–1038CrossRefGoogle Scholar
  52. 52.
    Tsvetkov PO, Kulikova AA, Golovin AV, Tkachev YV, Archakov AI (2010) Biophys J 99:L84–L86CrossRefGoogle Scholar
  53. 53.
    Davies P, Marken F, Salter S, Brown DR (2009) Biochemistry 48:2610–2619CrossRefGoogle Scholar
  54. 54.
    Brazier MW, Davies P, Player E, Marken F, Viles JH (2008) J Biol Chem 283:12831–12839CrossRefGoogle Scholar
  55. 55.
    Salamekh S, Brender R, Hyung SJ, Nanga RPR, Vivekanandan S, Ruotolo BT, Ramamoorthy A (2011) J Mol Biol 410:294–306CrossRefGoogle Scholar
  56. 56.
    Ross PD, Subramanian S (1981) Biochemistry 20:3096–3102CrossRefGoogle Scholar
  57. 57.
    Hu YJ, Ou-Yang YC, Dai M, Liu Y, Xiao XH (2010) Biomacromol 11:106–112CrossRefGoogle Scholar
  58. 58.
    Metcalfe C, Adams H, Haq I, Thomas JA (2003) Chem Commun 10:1152–1153CrossRefGoogle Scholar
  59. 59.
    Peng D, Tan J, Chen S, Ou T, Gu LQ (2010) Bioorg Med Chem 18:M8235–M8242CrossRefGoogle Scholar
  60. 60.
    Ma Q, Li Y, Du J, Liu H, Kanazawa K, Nemoto T, Nakanishi H, Zhao Y (2006) Peptides 27:841–849CrossRefGoogle Scholar
  61. 61.
    Soong R, Brender JR, Macdonald PM, Ramamoorthy A (2009) J Am Chem Soc 131:7079–7085CrossRefGoogle Scholar
  62. 62.
    Hebda JA, Saraogi I, Magzoub M, Hamilton AD, Miranker AD (2009) Chem Biol 16:943–950CrossRefGoogle Scholar
  63. 63.
    Bahramikia S, Yazdanparast R (2013) Eur J Pharmacol 707:17–25CrossRefGoogle Scholar
  64. 64.
    Grabenauer M, Wu C, Soto P, Shea JE, Bowers MT (2010) J Am Chem Soc 132:532–539CrossRefGoogle Scholar
  65. 65.
    Walsh P, Neudecke P, Sharpe S (2010) J Am Chem Soc 22:7684–7695CrossRefGoogle Scholar
  66. 66.
    Bartolini M, Bertucci C, Bolognesi ML, Cavalli A, Melchiorre C, Andrisano V (2007) Chem BioChem 172:152–2161Google Scholar
  67. 67.
    Zhao C, Wang X, He L, Zhu D, Wang B, Du W (2014) Metallomics 6:2117–2125CrossRefGoogle Scholar
  68. 68.
    Gong G, Wang W, Du W (2017) RSC Adv 7:18512–18522CrossRefGoogle Scholar
  69. 69.
    Du W, Gong G, Wang W, Xu J (2017) J Biol Inorg Chem 15:1065–1074CrossRefGoogle Scholar
  70. 70.
    Hebda JA, Saraogi I, Magzoub M, Hamilton AD, Miranker AD (2009) Chem Biol 16:943–950CrossRefGoogle Scholar
  71. 71.
    Ross PD, Subramanian S (1981) Biochemistry 20:3096–3102CrossRefGoogle Scholar
  72. 72.
    Hu Y, Yang Y, Dai C, Liu Y, Xiao X (2010) Biomacromol 11:106–112CrossRefGoogle Scholar
  73. 73.
    Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, Westermark P (2014) Amyloid 21:221–224CrossRefGoogle Scholar
  74. 74.
    Verchere CB, Natl P (1996) Acad Sci USA 93:3492–3496CrossRefGoogle Scholar
  75. 75.
    Brender JR, Lee EL, Cavitt MA, Gafni A, Steel DG (2008) J Am Chem Soc 130:6424–6429CrossRefGoogle Scholar
  76. 76.
    Bucciantini M, Valadie H, Bednarova L, Cardin L, Pasdeloup M, Cappadoro J, Bednar J, Rinaudo M (2002) Nature 416:507–511CrossRefGoogle Scholar

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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