Cyclen-hybrid compound captures copper to protect INS-1 cells from islet amyloid polypeptide cytotoxicity by inhibiting and lysing effects.
Human islet amyloid polypeptide (hIAPP) deposit is the hallmark of type 2 diabetes pathology. Here, we report that apo-cyclen, attached to a specific hIAPP recognition motif (NYGAIL), captured copper ions and became proteolytically active. This cyclen-NYGAIL-copper complex was able to interfere with hIAPP aggregation and cleave hIAPP. These activities rescued INS-1 cells from hIAPP induced cytotoxicity.
Hu
Jia
J
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China.
Yu
Ye-Ping
YP
Cui
Wei
W
Fang
Chuan-Lin
CL
Wu
Wei-Hui
WH
Zhao
Yu-Fen
YF
Li
Yan-Mei
YM
D002460:Cell Line; D003300:Copper / Q000737:chemistry*; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000633:toxicity*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000080027:Cyclams; D006571:Heterocyclic Compounds; D058228:Islet Amyloid Polypeptide; D003300:Copper; C038072:cyclen