Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 706-717 |
| Number of pages | 12 |
| Journal | ACS chemical biology |
| Volume | 15 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 20 2020 |
Funding
R.C.B. was supported in part by the Chicago Cancer Baseball Charities at the Lurie Cancer Center of Northwestern University and the NIGMS Chemical-Biology Interface T32 Training Grant GM105538. Y.L. and S.J.K. were supported by NIH R01 CA217182. S.B.C acknowledges support from the Ernest & Piroska Major Foundation and Kids Cancer Alliance (Australia). The authors thank M. Iorio at NAICONS Laboratories, Milan Italy, for providing Actinomycete Actinospica for chrolactomycin isolation and E. Skordalakes at the Wistar Institute, Philadelphia PA, for generously providing tcTERT.
ASJC Scopus subject areas
- Molecular Medicine
- Biochemistry
