cb9b00945_si_001.pdf (17.88 MB)
Targeted Covalent Inhibition of Telomerase
journal contribution
posted on 2020-02-24, 15:37 authored by Rick C. Betori, Yue Liu, Rama K. Mishra, Scott B. Cohen, Stephen J. Kron, Karl A. ScheidtTelomerase
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 noncanonical extra-telomeric roles in oncogenic signaling,
resistance to apoptosis, and enhanced DNA damage response. We report
a new class of natural-product-inspired covalent inhibitors of telomerase
that target the catalytic active site.