Can AZT be phosphorylated?
Under identical conditions, AZT is phosphorylated only to AZT-5′-monophosphate (AZT-MP). The kinetics of thymidine and AZT suggest negative cooperativity of substrate interaction with the enzyme, consistent with work by others on mitochondrial thymidine kinase 2.
What is AZT and how does it work?
AZT belongs to a group of drugs called nucleoside analogues. AZT interferes with an enzyme called reverse transcriptase (RT), which is used by HIV-infected cells to make new viruses. Since AZT inhibits, or reduces the activity of this enzyme, this drug causes HIV-infected cells to produce fewer viruses.
How does AZT stop DNA replication?
3. 1 AZT causes replication inhibition and SOS induction via accumulation of single-strand DNA gaps. If AZT causes DNA damage by inhibiting replication fork progression, replication should stop or slow when cultures are treated with AZT.
How is AZT activated?
Nucleoside-based inhibitors of reverse transcriptase were the first drugs to be used in the chemotherapy of AIDS. After entering the cell, these substances are activated to their triphosphate form by cellular kinases, after which they are potent chain terminators for the growing viral DNA.
Why is AZT a competitive inhibitor?
AZT-5′-triphosphate (AZTTP) is a known inhibitor of the mitochondrial DNA polymerase gamma and has been targeted as the source of the mitochondrial DNA depletion. In both of these tissues, AZT was found to be a competitive inhibitor of the phosphorylation of thymidine to TMP, catalyzed by thymidine kinase 2.
What type of inhibitor is AZT?
AZT is an analog of the thymidine deoxynucleoside and is a member of the class called the nucleoside-analog reverse transcriptase inhibitors. AZT and other members of this class function by inhibiting the HIV reverse transcriptase. This halts the life cycle of the virus and slows the progression of AIDS.
Is AZT harmful?
It is concluded that AZT, at the dosage prescribed as an anti-HIV drug, is highly toxic to human cells.
How is AZT Zidovudine synthesis?
Zidovudine is 3′-azido-3′-deoxytimidine (36.1. 26), is synthesized from 1-(2′-deoxy-5′-O-trityl-β-d-lyxosyl)thymine, which is treated with methansulfonyl chloride in pyridine to make the corresponding mesylate 36.1. 24.
Is AZT a competitive inhibitor?
Since AZT is functioning as a competitive inhibitor, increasing thymidine concentrations may be one mechanism to overcome the inhibition and decrease AZT-related toxicity in these tissues.
Is AZT nucleophilic or electrophilic?
Answer: Subsequent growth of cDNA is not possible because the azide group on AZT is A. not nucleophilic/not Lewis basic.
Why is subsequent growth of cDNA not possible?
Viral DNA replication stops since the azide group is a poor nucleophile unlike the -OH group. Answer: Subsequent growth of cDNA is not possible because the azide group on AZT is A. not nucleophilic/not Lewis basic.
Is azide a good leaving group?
Acyl azides are activated carboxylate groups that can react with primary amines to form amide bonds. The azide function is a good leaving group similar to the N-hydroxysuccinimide group of NHS ester compounds.