Polypeptide induced perylene probe excimer formation and its application in the noncovalent ratiometric detection of matrix metalloproteinase activity. Issue 30 (20th July 2022)

• Record Type: Journal Article
• Authors: Gou, Xiaoyu; Nawaz, Muhammad Azhar Hayat; Liu, Chaoyi; Yang, Na; Ren, Jia; Zhou, Huipeng; Li, Yunhui; Zhu, Jianwei; Han, Wenzhao; Yu, Cong
• Is Part Of: Journal of materials chemistry. Volume 10:Issue 30(2022)
• Page Start: 5774
• Page End: 5783
• Publication Date: 2022-07-20
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/d2tb00416j
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : This research develops a novel ratiometric strategy based on a perylene derivative (PC1) monomer/excimer fluorescence signal transition to detect MMP activity and to screen for potential inhibitors. Abstract : Matrix metalloproteinases (MMPs) are important biomarkers for a number of diseases. Thus, the precise determination of MMP activity is of crucial importance. Herein, we report a ratiometric fluorescence method for the sensitive and selective sensing of MMP activity. A number of positively charged MMP substrates (polypeptides) were designed and prepared. These polypeptides could induce aggregation of a negatively charged perylene diimide derivative (PC1). As a result, excimer fluorescence of PC1 was observed. Addition of the corresponding MMP resulted in cleavage of the polypeptide chain and dis-aggregation of PC1, which led to turning on of the PC1 monomer fluorescence. Based on the ratio of the monomer (545 nm, I M ) and the excimer (680 nm, I M ) fluorescence intensity changes, a ratiometric method I 545 / I 680 ) was established to detect MMP activity. The enzymatic activity of a number of MMPs (MMP-1, 2, 3, 7, 9 and 13) could be determined with a limit of detection of 4.8, 2.2, 16, 6.0, 1.7 and 5.5 ng mL −1, respectively. Using MMP-2 and MMP-9 as examples, flavonoid herbal extracts as potential inhibitors were studied. It was observed that mangiferin, apigenin, quercetin and isoliquiritigenin had significant inhibiting effects on the enzyme activity. And these herbal extracts also inhibited tumor cell metastasis. Moreover, the developed strategy was also employed to determine the concentration of MMP-9 in human saliva samples. Since the method relies on only noncovalent interactions between the polypeptide and PC1, no covalent labeling of fluorescence dye on the polypeptide substrate is required, and the method is thus simple, broad-spectrum inexpensive and effective. It has the potential to be developed into a clinical test kit.