Kevin Pels, Paige Dickson, Hongchan An, and Thomas Kodadek
ACS Comb. Sci., 2018
DOI: 10.1021/acscombsci.7b00169
We demonstrate that the Knoevenagel condensation can be exploited in combinatorial synthesis on the solid phase. Condensation products from such reactions were structurally characterized, and their Michael reactivity with thiol and phosphine nucleophiles is described. Cyanoacrylamides were previously reported to react reversibly with thiols, and notably, we show that dilution into low pH buffer can trap covalent adducts which are isolable via chromatography. Finally, we synthesized both traditional and DNA-encoded one-bead, one-compound libraries containing cyanoacrylamides as a source of cysteine-reactive, reversibly covalent protein ligands.
A blog highlighting recent publications in the area of covalent modification of proteins, particularly relating to covalent-modifier drugs. @CovalentMod on Twitter, @covalentmod@mstdn.science on Mastodon, and @covalentmod.bsky.social on BlueSky
Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders
Nathanael Schiander Gray , Zhe Zhuang , Woong Sub Byun , Zuzanna Kozicka , Katherine Donovan , Brendan Dwyer , Abby Thornhill , Hanna...
-
Design, synthesis and biological evaluation of the activity-based probes for FGFR covalent inhibitorDandan Zhu, Zijian Zheng, Huixin Huang, Xiaojuan Chen, Shuhong Zhang, Zhuchu Chen, Ting Liu, Guangyu Xu, Ying Fu, Yongheng Chen, European Jo...
-
DOI Ansgar Oberheide, Maxime van den Oetelaar, Jakob Scheele, Jan Borggräfe, Semmy Engelen, Michael Sattler, Christian Ottmann, ...
-
George S. Biggs, Emma E. Cawood, Aini Vuorinen, William J. McCarthy, Harry Wilders, Ioannis G. Riziotis, Antonie J. van der Zouwen, Jonathan...