Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois 60637, United States.
ACS Chem Biol. 2020 Mar 20;15(3):706-717. doi: 10.1021/acschembio.9b00945. Epub 2020 Feb 24.
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.
端粒酶是一种核糖核蛋白复合物，负责维持端粒并保护染色体的完整性。人类端粒酶逆转录酶（hTERT）在约 90%的癌细胞中表达，赋予其无限增殖的能力。除了在端粒延长中的既定作用外，端粒酶还在致癌信号、抗凋亡和增强的 DNA 损伤反应中发挥非典型的端粒外作用。我们报告了一类新型的受天然产物启发的端粒酶共价抑制剂，其靶向催化活性位点。
