Synthesis of a β-Arylethenesulfonyl Fluoride-Functionalized AIEgen for Activity-Based Urinary Trypsin Detection

Abstract

Trypsin is one of the most important enzymes of the digestive system produced by the pancreatic acinar cells. Abnormal trypsin activity will affect pancreatic function, resulting in the corresponding pathological changes in the human body. Herein, we present a strategy based on the ensemble of a novel dual warhead probe HPC-ESF and the natural trypsin substrate bovine serum albumin (BSA) for the detection of trypsin activity including in real urine samples. The β-arylethenesulfonyl bearing HPC-ESF is nonemissive when dissolved in aqueous solution but becomes highly fluorescent upon conjugation to BSA through covalent bond formation with nucleophilic amino acids to create the HPC-ESF:BSA sensing system. The HPC-ESF:BSA complex can be hydrolyzed in the presence of trypsin, which results in a distinct fluorescence decrease in correlation with trypsin concentration and thus allows the detection of trypsin. Compared to previous methods, our covalent approach is simple to prepare and highly reliable. Our work will provide a different avenue for researchers to design fluorescent sensors based on a covalent labeling strategy, enriching the small library of functional groups available for such applications.

Molecular Design and Biomedical Application of AIEgens with Photochemical Activity

“…11 Furthermore, most AIEgens can be simply synthesized and modified to achieve multifunctionalities and superior properties such as intense emission, large Stokes shift, good photostability, and excellent biocompatibility, which make them great candidates in biomedical areas. Up to now, various AIEgens have been developed for application in chemical sensing, 12,13 bioimaging, 14,15 photodynamic/photothermal therapy, 16−19 etc. Multifunctional materials that integrate the advantages of AIE and photochemical activity in a single formulation for synchronous biomedical applications are highly desired, which can be employed in photoactivation imaging, super-resolution imaging, photodynamic therapy, etc (Scheme 1A, right).…”

Ultrasensitive Determination of Trypsin in Human Urine Based on Amplified Fluorescence Response

“…3,4 For example, in the urine of healthy people, trypsin is present at low concentrations (0.115−0.350 μg mL −1 ), whereas in patients with acute pancreatitis, average concentrations exceed 84.4 μg mL −1 . 5,6 In addition, the concentration of trypsin in urine is related to the activities of trypsin inhibitors and is used to determine the presence of renal or genitourinary infections. 7,8 Thus, changes in the activities of trypsin and/or trypsin inhibitors in urine can serve as diagnostic biomarkers of pancreatic diseases.…”

“…However, it is also involved in pathological processes such as inflammation and cancer and can cause tissue damage. , In particular, when trypsinogen (the precursor of trypsin) is activated prematurely in the pancreas, the trypsin produced damages pancreatic exocrine cells and enters blood and urine. Furthermore, increases in trypsin concentrations in these body fluids are associated with pancreatitis, cystic fibrosis, and related diseases. , For example, in the urine of healthy people, trypsin is present at low concentrations (0.115–0.350 μg mL –1 ), whereas in patients with acute pancreatitis, average concentrations exceed 84.4 μg mL –1 . , In addition, the concentration of trypsin in urine is related to the activities of trypsin inhibitors and is used to determine the presence of renal or genitourinary infections. , Thus, changes in the activities of trypsin and/or trypsin inhibitors in urine can serve as diagnostic biomarkers of pancreatic diseases.…”

A diversity oriented clicking strategy: the stereoselective synthesis of highly-functionalised olefins from 2-substituted-alkynyl-1-sulfonyl fluorides

“…1,2 DOC merges the benefits of classical click chemistry 3 with the versatility of connective SuFEx hubs (see Fig. 1(A) for selected SuFEx hub examples), 4–24 enabling the discovery of diverse lead-like molecules using robust and reliable click transformations.…”