PMID- 33164004
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20201113
LR  - 20201113
IS  - 1364-5528 (Electronic)
IS  - 0003-2654 (Linking)
VI  - 145
IP  - 22
DP  - 2020 Nov 9
TI  - Mechanism study on the abnormal accumulation and deposition of islet amyloid 
      polypeptide by cold-spray ionization mass spectrometry.
PG  - 7289-7296
LID - 10.1039/d0an01034k [doi]
AB  - The abnormal accumulation and deposition of islet amyloid polypeptide (IAPP) are 
      important causes of type-2 diabetes mellitus (T2DM). The common anti-amyloid 
      strategy employs inhibitors to prevent the formation of oligomers and the 
      cytotoxicity caused by them, thus reducing the production of amyloid fibres. 
      Therefore, the real characterization of the oligomers formed at the early stage 
      of aggregation is crucial to understanding the structure of IAPP and the drug 
      development of T2DM. For the first time, in this study, native cold-spray 
      ionization mass spectrometry (CSI-MS) technology was employed to characterize the 
      oligomers. It was found that CSI was more suitable for the determination of these 
      unstable species compared to traditional ESI-MS. The ionic strengths, organic 
      solvent and pH all had effects on the characterization of oligomers and the 
      stability of protein conformation. The MS/MS experiments showed that odd-charge 
      dimer ions were mainly composed of two monomer products. Moreover, a CSI-MS 
      method for the rapid screening of IAPP-inhibitors was established and two of the 
      most potential inhibitors (rutin and quercitrin) were screened from a series of 
      flavonoids. Then, the structure-activity relationship and the mechanism between 
      flavonoids and IAPP were studied. The results showed that 3-OH and sugar chains 
      play a vital role and hydrogen bonds are the main binding force. We further 
      confirmed that rutin and quercitrin could effectively inhibit the fibre formation 
      of IAPP by fluorescence and TEM experiments. This study provides a new insight 
      for analyzing the structure of IAPP and screening potential drugs for T2DM.
FAU - Chen, Su
AU  - Chen S
AD  - Key Laboratory of Theoretical and Computational Photochemistry, Ministry of 
      Education, College of Chemistry, Beijing Normal University, Beijing, 100875, 
      China. jinoyang@bnu.edu.cn.
FAU - Liu, Yang
AU  - Liu Y
FAU - Zhou, Yanan
AU  - Zhou Y
FAU - He, Lan
AU  - He L
FAU - Ouyang, Jin
AU  - Ouyang J
LA  - eng
PT  - Journal Article
PL  - England
TA  - Analyst
JT  - The Analyst
JID - 0372652
SB  - IM
EDAT- 2020/11/10 06:00
MHDA- 2020/11/10 06:01
CRDT- 2020/11/09 05:36
PHST- 2020/11/09 05:36 [entrez]
PHST- 2020/11/10 06:00 [pubmed]
PHST- 2020/11/10 06:01 [medline]
AID - 10.1039/d0an01034k [doi]
PST - ppublish
SO  - Analyst. 2020 Nov 9;145(22):7289-7296. doi: 10.1039/d0an01034k.