Open AccessTargeted Covalent Inhibition of Telomerase
Author(s) -
Rick C. Betori,
Yue Liu,
Rama K. Mishra,
Scott Cohen,
Stephen J. Kron,
Karl A. Scheidt
Publication year - 2020
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.9b00945
Subject(s) - telomerase , telomere , telomerase reverse transcriptase , reverse transcriptase , dna , dna damage , microbiology and biotechnology , biology , cancer research , chemistry , genetics , gene , rna
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.