Handout #6 ANSWERS

Handout #6 ANSWERS - Handout #6- ANSWERS 1. Dr. Urnov...

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Handout #6- ANSWERS 1. Dr. Urnov talked about the molecule 2´-deoxy-2´,2´-difluorocytidine in his 2/27 lecture. What does this molecule do and how does it do it? a. This molecule is used as an anticancer drug. It was discovered by the pharmaceutical company Eli Lilly and Company, and is marketed under the brand name Gemzar. It is a nucleoside metabolic inhibitor. Because its structure closely matches that of other nucleosides, enzymes such as DNA polymerase will incorporate it into DNA as it is being replicated, resulting in early termination of the DNA strand after one more nucleotide is added by DNA polymerase. The article “Cellular pharmacology of gemcitabine” (Annals of Oncology 17 (Supplement 5): v7–v12, 2006) summarizes its activity: “Following influx through the cell membrane via nucleoside transporters, gemcitabine undergoes complex intracellular conversion to the nucleotides gemcitabine diphosphate (dFdCDP) and triphosphate (dFdCTP) responsible for its cytotoxic actions. The cytotoxic activity of gemcitabine may be the result of several actions on DNA synthesis. dFdCTP competes with deoxycytidine triphosphate (dCTP) as an inhibitor of DNA polymerase. dFdCDP is a potent inhibitor of ribonucleoside reductase, resulting in depletion of deoxyribonucleotide pools necessary for DNA synthesis and, thereby potentiating the effects of dFdCTP. dFdCTP is incorporated into DNA and after the incorporation of one more nucleotide leads to DNA strand termination. This extra nucleotide may be important in hiding the dFdCTP from DNA repair enzymes, as incorporation of dFdCTP into DNA appears to be resistant to the normal mechanisms of DNA repair.” 2.
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Handout #6 ANSWERS - Handout #6- ANSWERS 1. Dr. Urnov...

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