PMID- 30149123
OWN - NLM
STAT- MEDLINE
DCOM- 20190610
LR  - 20190613
IS  - 1873-3344 (Electronic)
IS  - 0162-0134 (Linking)
VI  - 189
DP  - 2018 Dec
TI  - Regulation of heteronuclear Pt-Ru complexes on the fibril formation and 
      cytotoxicity of human islet amyloid polypeptide.
PG  - 7-16
LID - S0162-0134(18)30205-8 [pii]
LID - 10.1016/j.jinorgbio.2018.08.012 [doi]
AB  - The deposition of human islet amyloid polypeptide (hIAPP) is considered as a 
      causative factor of type 2 diabetes mellitus (T2DM). Developing effective 
      inhibitors against the fibril formation of hIAPP is a potential way to treat 
      T2DM. Recent studies indicate that various metal complexes including 
      homo-binuclear Ru complexes can inhibit hIAPP aggregation. Hetero-multinuclear 
      PtRu metal complexes exhibit multiple bioactivities, but their roles in reversing 
      amyloidosis remain unclear. In this work, we synthesized and identified a new 
      hetero-binuclear PtRu metal complex Na[RuCl(4)(DMSO-S)](bpy)[Pt(DMSO-S)Cl(2)] 
      (bpy: 4,4'-bipyridyl). We studied the inhibitory effect of the compound on hIAPP 
      aggregation together with K[RuCl(4)(DMSO-S)](pyz)[Pt (DMSO-S)Cl(2)] (pyz: 
      pyrazine) through diverse biophysical methods. Results showed that two PtRu metal 
      complexes can remarkably reverse hIAPP aggregation and scatter the fibrils into 
      nanoscale particles. Thermodynamic and spectrometric studies revealed that the 
      binding of metal complexes with hIAPP was a spontaneous, enthalpy-driven process 
      resulting from the predominant hydrophobic interaction and metal coordination. 
      Two hetero-binuclear PtRu metal complexes showed stronger binding affinity and 
      better inhibitory effects against peptide fibril formation than homo-binuclear Ru 
      complexes and corresponding mononuclear Ru complexes. The compounds also 
      regulated the peptide-induced cytotoxicity against Insulinoma beta-cells and 
      significantly increased the cell viability. This work shed light on a potential 
      strategy for designing hetero-multinuclear metal complexes against 
      amyloidosis-related diseases.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Gong, Gehui
AU  - Gong G
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Du, Weihong
AU  - Du W
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China. 
      Electronic address: whdu@ruc.edu.cn.
FAU - Xu, Jufei
AU  - Xu J
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Huang, Xiangyi
AU  - Huang X
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Yin, Guowei
AU  - Yin G
AD  - College of Physicians & Surgeons, Columbia University, New York, NY, United 
      States of America; Division of Molecular Therapeutics, New York State Psychiatric 
      Institute, New York, NY, United States of America. Electronic address: 
      gy2265@cumc.columbia.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180818
PL  - United States
TA  - J Inorg Biochem
JT  - Journal of inorganic biochemistry
JID - 7905788
RN  - 0 (Amyloid)
RN  - 0 (Coordination Complexes)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 49DFR088MY (Platinum)
RN  - 7UI0TKC3U5 (Ruthenium)
SB  - IM
MH  - Amyloid/chemistry
MH  - Coordination Complexes/*chemistry
MH  - Humans
MH  - Islet Amyloid Polypeptide/*chemistry
MH  - Platinum/*chemistry
MH  - Ruthenium/*chemistry
OTO - NOTNLM
OT  - Fibril formation
OT  - Heteronuclear PtRu complexes
OT  - Inhibition
OT  - hIAPP
EDAT- 2018/08/28 06:00
MHDA- 2019/06/14 06:00
CRDT- 2018/08/28 06:00
PHST- 2018/04/09 00:00 [received]
PHST- 2018/08/11 00:00 [revised]
PHST- 2018/08/15 00:00 [accepted]
PHST- 2018/08/28 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2018/08/28 06:00 [entrez]
AID - S0162-0134(18)30205-8 [pii]
AID - 10.1016/j.jinorgbio.2018.08.012 [doi]
PST - ppublish
SO  - J Inorg Biochem. 2018 Dec;189:7-16. doi: 10.1016/j.jinorgbio.2018.08.012. Epub 
      2018 Aug 18.