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A Near‐Infrared‐Controllable Artificial Metalloprotease Used for Degrading Amyloid‐β Monomers and Aggregates
Author(s) -
Ma Mengmeng,
Wang Ying,
Gao Nan,
Liu Xinping,
Sun Yuhuan,
Ren Jinsong,
Qu Xiaogang
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902828
Subject(s) - chemistry , hydrolysis , metalloproteinase , monomer , proteolysis , combinatorial chemistry , enzyme , biophysics , biochemistry , polymer , organic chemistry , biology
Proteolysis of amyloid‐β (Aβ) is a promising approach against Alzheimer's disease. However, it is not feasible to employ natural hydrolases directly because of their cumbersome preparation and purification, poor stability, and hazardous immunogenicity. Therefore, artificial enzymes have been developed as potential alternatives to natural hydrolases. Since specific cleavage sites of Aβ are usually embedded inside the β‐sheet structures that restrict access by artificial enzymes, this strongly hinders their efficiency for practical applications. Herein, we construct a NIR (near‐IR) controllable artificial metalloprotease (MoS 2 ‐Co) using a molybdenum disulfide nanosheet (MoS 2 ) and a cobalt complex of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (Codota). Evidenced by detailed experimental and theoretical studies, the NIR‐enhanced MoS 2 ‐Co can circumvent the restriction by simultaneously inhibition of β‐sheet formation and destroying β‐sheet structures of the preformed Aβ aggregates in living cell. Furthermore, our designed MoS 2 ‐Co is an easy to graft Aβ‐target agent that prevents misdirected or undesirable hydrolysis reactions, and has been demonstrated to cross the blood brain barrier. This method can be adapted for hydrolysis of other kinds of amyloids.