Inhibition of reverse transcriptase of human immunodeficiency virus type 1 and chimeric enzymes of human immunodeficiency viruses types 1 and 2 by two novel non-nucleoside inhibitors.
We have studied the effects of two non-nucleoside reverse transcriptase inhibitors (NNRTI), nitrophenyl phenyl sulfone (NPPS) and a potent derivative of oxathiin carboxanilide (UC-38), on enzymatically active molecular chimeras composed of complementary segments of the reverse transcriptases (RTs) of human immunodeficiency virus type 1 (HIV-1) and -2 (HIV-2). The substances inhibit only the DNA polymerase activity of HIV-1 RT with no effect on HIV-2 RT. The results suggest that there is a protein segment located between residues 158 and 190 that is critical for the inhibition by both compounds. However, there is probably a second segment that resides between residues 192 and 202, as in the case of NPPS, or residues 203 and 224, as in the case of UC-38, that is also crucial for the sensitivity of HIV-1 RT to both inhibitors.
Rubinek
T
T
Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
McMahon
J B
JB
Hizi
A
A
D000998:Antiviral Agents / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology; D015498:HIV-2 / Q000201:enzymology; D012194:RNA-Directed DNA Polymerase; D011993:Recombinant Fusion Proteins; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000494:pharmacology*; D013859:Thiocarbamates / Q000494:pharmacology*
D000998:Antiviral Agents; D001565:Benzoates; D011993:Recombinant Fusion Proteins; D018894:Reverse Transcriptase Inhibitors; D013450:Sulfones; D013859:Thiocarbamates; C083308:NSC 629243; C089033:2'-nitrophenylphenylsulfone; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase