Long, M.J.C.; Kulkarni, A.; Aye, Y. Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design? ChemBioChem 2021, 23, doi:10.1002/cbic.202100051.
Long, M.J.C.; Kulkarni, A.; Aye, Y. Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design? ChemBioChem 2021, 23, doi:10.1002/cbic.202100051.
Long, M.J.C.; Kulkarni, A.; Aye, Y. Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design? ChemBioChem 2021, 23, doi:10.1002/cbic.202100051.
Long, M.J.C.; Kulkarni, A.; Aye, Y. Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design? ChemBioChem 2021, 23, doi:10.1002/cbic.202100051.
Abstract
For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.
Keywords
electrophile signaling; cysteine; LDE; HNE; T-REX
Subject
Medicine and Pharmacology, Medicine and Pharmacology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
