Optimization of fluorescent substrates for ADAM17 and their utility in the detection of diabetes

• DOI: 10.1016/j.ab.2023.115337
• Publication Date: 2023-09-30T07:35:03Z
• Authors: Honorata Sikora; Natalia Gruba; Magdalena Wysocka; Agnieszka Piwkowska; Adam Lesner
• Keywords: Proteolysis; Diabetes Mellitus; Humans; Membrane Proteins; ADAM17 Protein; 3. Good health

ADAM17 (a disintegrin and metalloproteinase 17) is a sheddase that releases various types of membrane-associated proteins, including adhesive molecules, cytokines and their receptors, and inflammatory mediators. Evidence suggests that the enzyme is involved in the proteolytic cleavage of antiaging transmembrane protein Klotho (KL). What is more, reduced serum and urinary KL levels are observed in the early stages of chronic kidney disease. This study aimed to optimise the ADAM17 specific and selective fluorescent substrates. Then, the obtained substrate was used to detect the enzyme in urine samples of patients diagnosed with diabetes. It turned out that in all cases we were able to detect proteolytic activity, which was the opposite of the healthy samples.