Assays for alkaline phosphatase that use L-ascorbic acid 2-phosphate as a substrate

Alkaline phosphatase (ALP) is a zinc-containing metalloprotein widely distributed in mammalian tissues that catalyzes the dephosphorylation of a wide variety of phosphorylated species and plays a vital role in clinical diagnosis. First, ALP is one of the most widely used biocatalysts for signal amplification in the field of enzyme-linked assays. And what’s more, ALP is also a promising biomarker for disease diagnosis, whose abnormal level is closely associated with a series of diseases such as bone diseases and liver dysfunction. In view of the great significance of ALP in clinical diagnosis, the development of assays for sensitive and selective detection of ALP activity is urgently required. Recently, a very large number of well-designed assays for ALP activity that use L-ascorbic acid 2-phosphate (AAP) as a substrate have been developed, in which ALP catalyzes the hydrolysis of AAP to produce AA in situ, then the as-produced AA initiates a series of reactions, such as AA-mediated silver deposition, AA-triggered Cu+-catalyzed azide/alkyne cycloaddition, AA-triggered reduction of Fe3+, AA-triggered decomposition of MnO2 nanosheets, AA-triggered iodine-mediated etching, and AA-triggered redox cycling, for signal generation. In this review, working principle of assays for ALP activity that use AAP as a substrate are summarized and elaborated in detail through reasonable classification as well as effective illustration of application examples to summarize and comment on their development and advances. We believe that this work will provide new insights into the construction of more advanced sensing platforms for ALP activity detection with ultrahigh sensitivity, good selectivity, as well as excellent adaptability to a broad range of clinical diagnosis needs.