Saturday, November 23, 2019

Use of Pyridazinediones as Extracellular Cleavable Linkers Through Reversible Cysteine Conjugation

Calise Bahou , Richard Spears , Abil Aliev , Antoine Maruani , Marcos Fernandez , Faiza Javaid , Peter Szijj , James Baker and Vijay Chudasama

Chem. Commun. 2019
DOI: 10.1039/C9CC08362F

Herein we report a retro-Michael deconjugation pathway of thiol-pyridazinedione linked protein bioconjugates to provide a novel cleavable linker technology. We demonstrate that the novel pyridazinedione linker does not suffer from off-target modification with blood thiols (e.g. glutathione, human serum albumin (HSA)), which is in sharp contrast to an analogous maleimide linker.

Oncogenic KRAS G12C: Kinetic and Redox Characterization of Covalent Inhibition

Minh V. Huynh, Derek Parsonage, Tom E. Forshaw, Venkat R. Chirasani, G. Aaron Hobbs, Hanzhi Wu, Jingyun Lee, Cristina M. Furdui, Leslie B. P...