The abnormal fibrillation of human islet amyloid polypeptide (hIAPP) has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (-)-epigallocatechin gallate (EGCG) is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III)/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III) and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III) and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III) could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III)/EGCG complex in molar ratio of 1 : 1 asAl(EGCG)(H2O)(2) could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.
[1]Fudan Univ, Dept Macromol Sci, State Key Lab Mol Engn Polymers, Shanghai 200433, Peoples R China.
[2]Shanghai Univ Tradit Chinese Med, Yueyang Hosp Integrated Tradit Chinese & Western, Shanghai 200437, Peoples R China.
[3]Fudan Univ, Dept Chem, Shanghai Key Lab Mol Catalysis & Innovat Mat, Collaborat Innovat Ctr Chem Energy Mat, Shanghai 200433, Peoples R China.
[4]Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia.
(8.0+极速模式)