PMID- 31493679
OWN - NLM
STAT- MEDLINE
DCOM- 20200710
LR  - 20200710
IS  - 1873-3344 (Electronic)
IS  - 0162-0134 (Linking)
VI  - 201
DP  - 2019 Dec
TI  - Assembly behavior of amylin fragment hIAPP19-37 regulated by Au(III) complexes.
PG  - 110807
LID - S0162-0134(19)30401-5 [pii]
LID - 10.1016/j.jinorgbio.2019.110807 [doi]
AB  - Human islet amyloid polypeptide (hIAPP, amylin) may self-aggregate and rupture 
      the membrane of beta cells, which is closely correlated with the pathogenesis of 
      type 2 diabetes mellitus (T2DM). Hence, suppressing amyloidogenic hIAPP may be 
      beneficial for the treatment of diabetes. As an important part of hIAPP, the 
      fragment hIAPP19-37 was studied in this work to explore their disaggregation and 
      cellular behavior regulation by some selected Au complexes, as follows: dichloro 
      diethyl dithiocarbamate Au complex [AuCl(2)(DDTC)] (1), dichloro pyrrolidine 
      dithiocarbamate Au complex [AuCl(2)(PDT)] (2), dichloro 
      4-4'-dimethyl-2,2'-bipyridyl Au(III) chloride [AuCl(2)(Me)(2)bpy]Cl (3), and 
      dichloro 4-4-di-tert-butyl-2,2'-bipyridyl Au(III) chloride 
      [AuCl(2)(t-Bu)(2)bpy]Cl (4). The peptide aggregation was observed and analyzed by 
      fluorescence assay, atomic force microscopy (AFM), dynamic light scattering (DLS) 
      and other methods. The assembly behaviors of hIAPP19-37 affected by the four Au 
      complexes indicated that these complexes could effectively inhibit the 
      fibrillation of the peptide and depolymerized the aged peptide into nanoscale 
      particles. These Au compounds also remarkably reduced membrane leakage and 
      cytotoxicity caused by peptide oligomers. An interaction study revealed that the 
      complexes were predominantly bound with hIAPP19-37 through hydrophobic and 
      electrostatic interactions, and metal coordination. The differences among various 
      complexes were compared according to their binding affinity, inhibitory effect, 
      and cellular behavior. Our study offers a potential path for the possible 
      utilization of Au compounds as amyloidosis inhibitors.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Huang, Xiangyi
AU  - Huang X
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Xu, Jufei
AU  - Xu J
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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190829
PL  - United States
TA  - J Inorg Biochem
JT  - Journal of inorganic biochemistry
JID - 7905788
RN  - 0 (Coordination Complexes)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Organogold Compounds)
RN  - 0 (Peptide Fragments)
RN  - 0 (Pyridines)
RN  - 4QD397987E (Histidine)
RN  - 7440-57-5 (Gold)
SB  - IM
MH  - Animals
MH  - Coordination Complexes/chemistry
MH  - Gold/chemistry
MH  - Histidine/chemistry
MH  - Humans
MH  - Insulin-Secreting Cells/drug effects
MH  - Islet Amyloid Polypeptide/*chemistry
MH  - Organogold Compounds/*chemistry/toxicity
MH  - Peptide Fragments/*chemistry
MH  - Polymerization
MH  - Protein Binding
MH  - Pyridines/chemistry
MH  - Rats
OTO - NOTNLM
OT  - Aggregation
OT  - Au(III) complex
OT  - Inhibition
OT  - Interaction
OT  - hIAPP19-37
EDAT- 2019/09/08 06:00
MHDA- 2020/07/11 06:00
CRDT- 2019/09/08 06:00
PHST- 2019/06/14 00:00 [received]
PHST- 2019/08/03 00:00 [revised]
PHST- 2019/08/23 00:00 [accepted]
PHST- 2019/09/08 06:00 [pubmed]
PHST- 2020/07/11 06:00 [medline]
PHST- 2019/09/08 06:00 [entrez]
AID - S0162-0134(19)30401-5 [pii]
AID - 10.1016/j.jinorgbio.2019.110807 [doi]
PST - ppublish
SO  - J Inorg Biochem. 2019 Dec;201:110807. doi: 10.1016/j.jinorgbio.2019.110807. Epub 
      2019 Aug 29.