Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?

Version 1 : Received: 2 March 2021 / Approved: 3 March 2021 / Online: 3 March 2021 (14:54:03 CET)

How to cite: Long, M.; Kulkarni, A.; Aye, Y. Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?. Preprints 2021, 2021030138 (doi: 10.20944/preprints202103.0138.v1). Long, M.; Kulkarni, A.; Aye, Y. Can Precision Electrophile Signaling Make a Meaningful and Lasting Impression in Drug Design?. Preprints 2021, 2021030138 (doi: 10.20944/preprints202103.0138.v1).

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

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.