Pyrrolobenzoxazepinone derivatives as non-nucleoside HIV-1 RT inhibitors: further structure-activity relationship studies and identification of more potent broad-spectrum HIV-1 RT inhibitors with antiviral activity.
PMID: 10543890
1999
Journal of medicinal chemistry
Abstract: Compared with the lead 6 and nevirapine, several of the synthesized compounds (PBOs 13a-d and PPOs 13i-k) displayed higher inhibitory activity against wild-type RT and clinically relevant mutant RTs containing the single amino acid substitutions L100I, K103N, V106A, Y181I, and Y188L.
3,4,5-Trisubstituted-1,2,4-4H-triazoles as WT and Y188L mutant HIV-1 non-nucleoside reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses.
Abstract: Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant.
Abstract: Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex.
Abstract: We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution.
Resistance to nevirapine of HIV-1 reverse transcriptase mutants: loss of stabilizing interactions and thermodynamic or steric barriers are induced by different single amino acid substitutions.
Abstract: Mutations Y181I and Y188L, on the other hand, conferred resistance to Nevirapine affecting both koff and kon values.
Abstract: The kinetic parameters governing the inhibition by Nevirapine of the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase have been determined by steady-state kinetic analysis with the wild-type enzyme and with mutant reverse transcriptases containing the single amino acid substitutions L100I, K103N, V106A, V179D, Y1
Simultaneous mutations at Tyr-181 and Tyr-188 in HIV-1 reverse transcriptase prevents inhibition of RNA-dependent DNA polymerase activity by the bisheteroarylpiperazine (BHAP) U-90152s.
Abstract: Construction and in vitro analysis of double mutants Y181I/Y188L and Y181C/Y188L of HIV-1 RT showed > 150-fold resistance to U-90152S.
Abstract: The bisheteroarylpiperazine (BHAP) U-90152S, a highly specific inhibitor (IC50, 0.29 +/- 0.01 microM) of HIV-1 RT, inhibited the recombinant Y181I and Y188L HIV-1 RT mutants with IC50 values of 3.6 +/- 0.15 microM and 0.71 +/- 0.02 microM, respectively.
Abstract: The replacement of either Tyr-181 or Tyr-188 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) by the corresponding HIV-2 RT a
Kinetic and mutational analysis of human immunodeficiency virus type 1 reverse transcriptase inhibition by inophyllums, a novel class of non-nucleoside inhibitors.
PMID: 7509800
1994
The Journal of biological chemistry
Abstract: A mutant enzyme in which tyrosine 188 was changed to leucine was cross-resistant to both inophyllum B and TIBO R82913, as was HIV type 2 reverse transcriptase.
Characterization of HIV-1 strains isolated from patients treated with TIBO R82913.
PMID: 7514016
1994
AIDS research and human retroviruses
Abstract: The drug-resistant strain in this patient emerged after 3 weeks of treatment and was due to the Y188L mutation in its RT.
Polymerase chain reaction (PCR) as a diagnostic tool in HIV infection.
PMID: 7519811
1994
Verhandelingen - Koninklijke Academie voor Geneeskunde van Belgie
Abstract: In HIV-1 isolates from TIBO R82913-treated patients we identified two amino acid mutations (V108I and Y188L) involved in resistance (more than 100-fold reduced sensitivity).
Kinetics of different human immunodeficiency virus type 1 reverse transcriptases resistant to human immunodeficiency virus type 1-specific reverse transcriptase inhibitors.
HIV mutation literature information.
PMID: 
1999
Journal of medicinal chemistry
Browser Board
Co-occurred Entities
Filtrator
ViMRT