PMID- 29986579
OWN - NLM
STAT- MEDLINE
DCOM- 20191223
LR  - 20191223
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 9
IP  - 11
DP  - 2018 Nov 21
TI  - The Inhibitory Effect of Hydroxylated Carbon Nanotubes on the Aggregation of 
      Human Islet Amyloid Polypeptide Revealed by a Combined Computational and 
      Experimental Study.
PG  - 2741-2752
LID - 10.1021/acschemneuro.8b00166 [doi]
AB  - Fibrillar deposits formed by the aggregation of the human islet amyloid 
      polypeptide (hIAPP) are the major pathological hallmark of type 2 diabetes 
      mellitus (T2DM). Inhibiting the aggregation of hIAPP is considered the primary 
      therapeutic strategy for the treatment of T2DM. Hydroxylated carbon nanoparticles 
      have received great attention in impeding amyloid protein fibrillation owing to 
      their reduced cytotoxicity compared to the pristine ones. In this study, we 
      investigated the influence of hydroxylated single-walled carbon nanotubes 
      (SWCNT-OHs) on the first step of hIAPP aggregation: dimerization by performing 
      explicit solvent replica exchange molecular dynamics (REMD) simulations. 
      Extensive REMD simulations demonstrate that SWCNT-OHs can dramatically inhibit 
      interpeptide beta-sheet formation and completely suppress the previously reported 
      beta-hairpin amyloidogenic precursor of hIAPP. On the basis of our simulation 
      results, we proposed that SWCNT-OH can hinder hIAPP fibrillation. This was 
      further confirmed by our systematic turbidity measurements, thioflavin T 
      fluorescence, circular dichroism (CD), transmission electron microscope (TEM), 
      and atomic force microscopy (AFM) experiments. Detailed analyses of 
      hIAPP-SWCNT-OH interactions reveal that hydrogen bonding, van der Waals, and 
      pi-stacking interactions between hIAPP and SWCNT-OH significantly weaken the 
      inter- and intrapeptide interactions that are crucial for beta-sheet formation. Our 
      collective computational and experimental data reveal not only the inhibitory 
      effect but also the inhibitory mechanism of SWCNT-OH against hIAPP aggregation, 
      thus providing new clues for the development of future drug candidates against 
      T2DM.
FAU - Mo, Yuxiang
AU  - Mo Y
AD  - State Key Laboratory of Surface Physics, Key Laboratory for Computational 
      Physical Science (Ministry of Education), Collaborative Innovation Center of 
      Advanced Microstructures, and Department of Physics , Fudan University , Shanghai 
      200433 , People's Republic of China.
AD  - College of Physical Science and Technology , Guangxi Normal University , 15 Yucai 
      Road , Guilin 541004 , People's Republic of China.
FAU - Brahmachari, Sayanti
AU  - Brahmachari S
AUID- ORCID: 0000-0002-5816-8805
AD  - Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of 
      Life Sciences , Tel Aviv University , Tel Aviv 69978 , Israel.
FAU - Lei, Jiangtao
AU  - Lei J
AD  - State Key Laboratory of Surface Physics, Key Laboratory for Computational 
      Physical Science (Ministry of Education), Collaborative Innovation Center of 
      Advanced Microstructures, and Department of Physics , Fudan University , Shanghai 
      200433 , People's Republic of China.
FAU - Gilead, Sharon
AU  - Gilead S
AD  - Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of 
      Life Sciences , Tel Aviv University , Tel Aviv 69978 , Israel.
FAU - Tang, Yiming
AU  - Tang Y
AD  - State Key Laboratory of Surface Physics, Key Laboratory for Computational 
      Physical Science (Ministry of Education), Collaborative Innovation Center of 
      Advanced Microstructures, and Department of Physics , Fudan University , Shanghai 
      200433 , People's Republic of China.
FAU - Gazit, Ehud
AU  - Gazit E
AD  - Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of 
      Life Sciences , Tel Aviv University , Tel Aviv 69978 , Israel.
FAU - Wei, Guanghong
AU  - Wei G
AUID- ORCID: 0000-0001-5814-3328
AD  - State Key Laboratory of Surface Physics, Key Laboratory for Computational 
      Physical Science (Ministry of Education), Collaborative Innovation Center of 
      Advanced Microstructures, and Department of Physics , Fudan University , Shanghai 
      200433 , People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180723
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Amyloid)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Nanotubes, Carbon)
SB  - IM
MH  - Amyloid/*metabolism/ultrastructure
MH  - Circular Dichroism
MH  - Computer Simulation
MH  - Diabetes Mellitus, Type 2/*metabolism/pathology
MH  - Humans
MH  - Hydroxylation
MH  - In Vitro Techniques
MH  - Inverted Repeat Sequences
MH  - Islet Amyloid Polypeptide/*metabolism/ultrastructure
MH  - Microscopy, Atomic Force
MH  - Microscopy, Electron, Transmission
MH  - Molecular Dynamics Simulation
MH  - *Nanotubes, Carbon
MH  - Protein Aggregation, Pathological/*metabolism/pathology
MH  - Protein Conformation, beta-Strand
OTO - NOTNLM
OT  - TEM experiment
OT  - human islet amyloid polypeptide
OT  - hydroxylated carbon nanotubes
OT  - inhibitory mechanism
OT  - protein aggregation
OT  - replica exchange molecular dynamics simulations
EDAT- 2018/07/11 06:00
MHDA- 2019/12/24 06:00
CRDT- 2018/07/11 06:00
PHST- 2018/07/11 06:00 [pubmed]
PHST- 2019/12/24 06:00 [medline]
PHST- 2018/07/11 06:00 [entrez]
AID - 10.1021/acschemneuro.8b00166 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2018 Nov 21;9(11):2741-2752. doi: 
      10.1021/acschemneuro.8b00166. Epub 2018 Jul 23.