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18 Cards in this Set

  • Front
  • Back
retroviral enzymes
1) RT
2) protease
3) integrase
RT activ
RNA dependent DNA polymerase
RNAse H activ
DNA dependent DNA polymerase
RNA dependent DNA polymerase
converts ssRNA genome to dsRNA:DNA hybrid
RNAse activ
hydrolizes RNA strand of dsRNA:DNA hybrid to generate ssDNA complementary to RNA genome of virus
DNA dependent DNA polymerase
converts ssDNA to dsDNA
NRTI's are prodrugs - why?

(nucleoside reverse transcriptase inhibitors)
the prodrug has low cytotoxicity prior to activation. (redox)
Common features of NRTI's
(nucleoside reverse transcriptase inhibitors)
sugar base; H2O solubility;
not substrate for CYP (cytochrome 450) and P-glycoprot
efflux pump (cytotox from MultiResistant cells)
liver detox
Mechanism of anti-HIV activity of NRTIs and ANPs

(acyclic nucleoside phosphonates)
DNA chain termination after they are incorporated into DNA

Competition with the natural dNTP substrates to be incorporated into growing DNA chain
Structures of NNRTIs
(non-nucleoside revers. TI)
hydrophobic molecules
metabolized by CYP3A4

Highly selective against HIV-1 strains (1000x more selective than AZT

Interact with a nonsubstrate binding site at HIV-1 RT
do not have typical nucleoside structure

do not need to be metabolized in the cell to display antiviral activity
BOTH NRTI and NNRTI target RT.
NRTI directly interacts with dNTP substrate binding site, NNRTI interact with nonsubstrate binding site at HIV-1 RT
NRTIs incorporate in growing viral DNA chain and act as DNA chain terminators.

NNRTIs are not incorp. in vDNA
select for HIV1 strains
both NRTI and NNRTI select HIV1 strain but AA changes in RT are diff
NRTI/NNRTI interact w/ cellular DNA polymerases.
catalytic activities of integrase
strand transfer
"cut vDNA"

2 deoxynucleotides are removed from 3'-end of vDNA
strand transfer
"paste vDNA into host DNA"