Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The (-) enantiomers of 2',3'-dideoxy-5-fluoro-3'-thiacytidine [(-)-FTC] and 2',3'-dideoxy-3'-thiacytidine [(-)-BCH-189] were recently shown to inhibit selectively human immunodeficiency viruses (HIV) and hepatitis B virus in vitro. In the current study, the potential for HIV type 1 (HIV-1) resistance to these compounds was evaluated by serial passage of the virus in human peripheral blood mononuclear cells and MT-2 cells in the presence of increasing drug concentrations. Highly drug-resistant HIV-1 variants dominated the replicating virus population after two or more cycles of infection. The resistant variants were cross-resistant to (-)-FTC, (-)-BCH-189, and their (+) congeners but remained susceptible to 2',3'-dideoxycytidine, 3'-azido-3'-deoxythymidine, 3'-fluoro-3'-deoxythymidine, 2',3'-dideoxyinosine, phosphonoformate, the TIBO compound R82150, and the bis(heteroaryl)piperazine derivative U-87201E. Reverse transcriptase derived from drug-resistant viral particles was 15- to 50-fold less susceptible to the 5'-triphosphates of FTC and BCH-189 compared with enzyme from parental drug-susceptible virus. DNA sequence analysis of the reverse transcriptase gene amplified from resistant viruses consistently identified mutations at codon 184 from Met (ATG) to Val (GTG or GTA) or Ile (ATA). Sequence analysis of amplified reverse transcriptase from a patient who had received (-)-BCH-189 therapy for 4 months demonstrated a mixture of the Met-184-to-Val (GTG) mutation and the parental genotype, indicating that the Met-184 mutation can occur in vivo.
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PMID:Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides. 768 16

We have cloned the gene encoding the rat serotonin-2 (5-HT2) receptor. The transcription unit is divided into three exons by two introns. The major 5-HT2 transcript is 5.62 kb in length and contains 1173 bases of 5'-untranslated region (5'-UTR) 1413 bases of open reading frame, and 3033 bases of 3'-UTR. Primer extension demonstrates one strong transcription initiation site 1173 nt from the start codon. Reverse transcriptase-polymerase chain reaction analysis indicates the presence of at least one additional minor site of transcription initiation 1355 nt from the start codon. There are ATA boxes 28 nt 5' to both the major and minor sites of transcription initiation. Functional promoter mapping was carried out in a transient transfection assay. This analysis reveals that there are negative attenuating elements between 2.5 and 2.3 kb from the initiation site and positive elements between 1100 and 200 nt from transcription initiation. Minimal promoter sequences are contained within 200 nt of the major site of transcription initiation. These findings suggest that the expression of the 5-HT2 receptor gene is regulated by a combination of positive and negative elements operating through the minimal promoter.
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PMID:Cloning and functional promoter mapping of the rat serotonin-2 receptor gene. 808 27