Ashwag S. Alanazi’s research while affiliated with Cardiff University and other places

... Triage of different phosphate-protecting groups allowed the identification of POM as the best prodrug enabling the inhibitor to enter the cell, efficiently unmask, and engage cellular SOCS2 covalently specifically via Cys111 modification. The low efficacy of aryloxy triester phosphoramidate prodrugs can be explained by the lower levels of expression of the enzymes that unmask these prodrugs in HeLa cells 46 . The design and validation methods described in this work exemplify a blueprint that could be in the future used to develop and evaluate other pYcontaining small molecules. ...

Reference:

Structure-based design of a phosphotyrosine-masked covalent ligand targeting the E3 ligase SOCS2

... In particular, the activation process of ProTide prodrugs tends to occur specifically in the liver due to the susceptibility of the ester bonds in the ProTide structures to cleavage by liver hydrolases and the resistance to pre-hepatic metabolism 21,22 . This strategy has also proven to be a powerful technology in the efficient intracellular delivery of various active molecules 23 . Most recently, a modular design platform for carboxypeptidase-targeting fluorescence probes was established based on ProTide chemistry (Fig. 1C) 24 . ...

Reference:

Thio-ProTide strategy: A novel H2S donor–drug conjugate (DDC) alleviates hepatic injury via innate lysosomal targeting