靶向端粒酶的共价抑制。
Targeted Covalent Inhibition of Telomerase.
机构信息
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois 60637, United States.
出版信息
ACS Chem Biol. 2020 Mar 20;15(3):706-717. doi: 10.1021/acschembio.9b00945. Epub 2020 Feb 24.
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.
摘要
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。
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