SPECIFIC-INHIBITION OF THE REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND THE CHIMERIC ENZYMES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 BY NONNUCLEOSIDE INHIBITORS

被引:84
作者
HIZI, A
TAL, R
SHAHARABANY, M
CURRENS, MJ
BOYD, MR
HUGHES, SH
MCMAHON, JB
机构
[1] NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK,MD 21702
[2] NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702
关键词
D O I
10.1128/AAC.37.5.1037
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have studied the effects of four nonnucleoside inhibitors, including the novel natural product inhibitor calanolide A, on molecular chimeras containing complementary segments of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptases (RTs). All four compounds specifically inhibited the DNA polymerase activity of HIV-1 RT but had no apparent effect on the RNase H activity of this enzyme or on the DNA polymerase or RNase H activity of HIV-2 RT. Three of these compounds showed the generally expected patterns of resistance and susceptibility with the various chimeric RTs. However, the inhibition patterns of the chimeric RTs by calanolide A provided evidence that there is a segment between residues 94 and 157 in HIV-1 RT that is critical for inhibition. However, the data also suggest that there may be a second segment located between amino acids 225 and 427 in HIV-1 RT that is also important for specifying susceptibility to the drug.
引用
收藏
页码:1037 / 1042
页数:6
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