Tuesday, January 9, 2018

DNA-compatible solid-phase combinatorial synthesis of β-cyanoacrylamides and related electrophiles

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.

Covalent drug discovery using sulfur(VI) fluoride exchange warheads

Huang Huang, Lyn H. Jones Expert Opinion on Drug Discovery , 2023 https://doi.org/10.1080/17460441.2023.2218642 Covalent drug discovery has ...