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As a leading supplier for ADC cytotoxin discovery and manufacture, BOC Sciences provides various toxins used as payloads to conjugate with antibodies to form ADCs. Telomeres are guanine-rich regions located at the ends of chromosomes and are essential for preventing aberrant recombination as well as protecting against exonucleolytic DNA degradation. Telomeres are maintained by telomerase, an RNA-dependent DNA polymerase. Because telomerase is known to expressed in tumor cells with short telomeres, while not in most somatic cells which usually have long telomeres, telomerase and telomere structures have been proposed as effective targets for the anti-cancer agents discovery recently. Currently, the most exciting strategies are aimed at specifically designing new drugs that target telomerase or telomeres, and new models have been formulated to study the biological effects of telomerase inhibitors and telomeres in vitro and in vivo.
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Human telomeres are simple (TTAGGG)n repeated sequences located at the ends of chromosomes. This structure capping the chromosome termini is essential to prevent aberrant recombination, protect chromosomes against exonucleolytic degradation, and gene regulation at distal loci. Evidence indicates that telomeric DNA shortens during the growth of various human somatic cells. Furthermore, cell senescence may occur due to checkpoint arrest in response to the shortened telomeres. The loss of telomeric repeats after each cell division may be a biological clock limiting the proliferative lifespan of somatic cells. To compensate sequence loss that results from incomplete terminal replication, germline cells, immortalized cells, and tumor cells express an RNA-dependent DNA polymerase. Telomerase is a ribonucleoprotein containing a short RNA motif that serves as a template for synthesizing telomeric DNA. Its expression is restricted to a few cell types of the adult organism, most notably germ cells and stem/progenitor cells. In cancer cells, Telomerase's activity is linked to telomere maintenance leading to unlimited cellular proliferation and immortality. Telomerase is up-regulated in most cancer cells and is essential for their survival, making it a potential anti-cancer drug target.
Anal. Chem. 2020, 92, 22, 15179–15186.
As a novel telomerase inhibitor, Telomestatin is also the most potent telomerase inhibitor so far. Telomestatin specifically inhibited telomerase without affecting reverse transcriptase and polymerases. In addition, Telomestatin induced telomere shortening, but in a must faster rate than physiological telomere shortening. Telomeres consist of guanine-rich sequences which compose a characteristic three-dimensional structure designated as G-quadruplex. Stabilization of G-quadruplex structure inhibited the catalysis of telomerase and other DNA interacting molecules. Thus, Telomestatin potently stabilized G-quadruplex structure in a specific manner. Nevertheless, G-quadruplex structure is also involved in many oncogene promoters, making Telomestatin a novel therapeutic molecular target for cancer chemotherapy.
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