期刊
BIOSENSORS & BIOELECTRONICS
卷 178, 期 -, 页码 -出版社
ELSEVIER ADVANCED TECHNOLOGY
DOI: 10.1016/j.bios.2021.113010
关键词
Electrochemical sensor; Matrix metalloproteinase; MMP-2 activity; Proteolytic cleavage; Ferrocenyl polymers; RAFT polymerization
类别
资金
- National Natural Science Foundation of China [21904026]
A novel electrochemical sensor is presented for highly specific interrogation of MMP activities at ultralow levels. The sensor is highly selective with a detection limit as low as 0.27 pg mL(-1) and a linear range from 1 pg mL(-1) to 1 ng mL(-1). Its applicability in complex serum samples and screening of MMP inhibitors is satisfactory, showing great promise in drug discovery and disease diagnosis.
Being closely associated with a variety of physiological and pathological processes, matrix metalloproteinases (MMPs) are useful as potential targets for drug therapy and informative markers for disease diagnosis. On the basis of the electrochemically induced grafting of ferrocenyl polymers and the proteolytic cleavage of recognition peptide, a novel electrochemical sensor is presented in this work for the highly specific interrogation of MMP activities at ultralow levels. The recognition peptide, to be immobilized via the N-terminus, is free of carboxyl group. The presence of the target MMP would cleave the end-tethered recognition peptide, generating a free carboxyl group at the C-terminus of the rest fragment. To be used as the reversible addition-fragmentation chain-transfer (RAFT) agent, the dithiobenzoate, 4-cyano-4-(phenylcarbonothioylthio)pentanoic acid (CPAD), can therefore be tethered via the carboxylate-Zr(IV)-carboxylate chemistry. Subsequently, the grafting of ferrocenyl polymers through electrochemically induced RAFT (eRAFT) polymerization of ferrocenylmethyl methacrylate (FcMMA) would recruit a large quantity of Fc redox reporters on electrode surface. With benefits from the excellent specificity of the enzyme-substrate recognition, the presented cleavage-based sensor is highly selective. Under optimal conditions, the detection limit in the presence of MMP-2 as the model target can be as low as 0.27 pg mL(-1), with a linear range from 1 pg mL(-1) to 1 ng mL(-1). Furthermore, its applicability in the interrogation of MMP activity in complex serum samples and the screening of MMP inhibitors is satisfactory. The presented cleavage-based electrochemical MMP sensor is easy to fabricate and low-cost, thus showing great promise in drug discovery and disease diagnosis.
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