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.

Thiol Reactivity of N-Aryl α-Methylene-γ-lactams: Influence of the Guaianolide Structure [@KayBrummond]

 Daniel P. Dempe, Chong-Lei Ji, Peng Liu, and Kay M. Brummond The Journal of Organic Chemistry, 2020 DOI: 10.1021/acs.joc.2c01530 The α-meth...