Targeted Covalent Inhibition of Telomerase

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 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.