Tuesday, July 23, 2019

Targeted Covalent Inhibition of Telomerase

Rick Betori, Yue Liu, Ding Wu, Rama Mishra, Scott Cohen, Stephen J. Kron, Karl Scheidt
ChemRxiv, 2019
doi: 10.26434/chemrxiv.8977457.v1

Telomerase is a ribonuceloprotein complex responsible for maintaining telomeres and protecting chromosomal integrity. The human telomerase reverse transcriptase (hTERT) is expressed in ~90% of cancer cells where it confers the capacity for limitless proliferation. Along with its established role in telomere lengthening, telomerase also serves non-canonical extra-telomeric roles in oncogenic signaling, resistance to apoptosis, and enhanced DNA damage response. Here, we report a new class of natural product-inspired covalent inhibitors of telomerase that target the catalytic active site. We developed rationally designed probe compounds that modulate both the telomeric and extra-telomeric activities of telomerase and present new opportunities to investigate the diverse functions of this unique molecular machine.

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...