Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nonapeptide H-Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 containing the retroviral Tyr-Pro cleavage site is a good substrate for the proteinase of human immunodeficiency viruses but it is not readily hydrolyzed by other nonviral proteinases including the structurally related pepsin-like aspartic proteinases. Replacing the Pro by L-pipecolic acid (2-piperidinecarboxylic acid) converted the substrate into an effective inhibitor of HIV-1 and HIV-2 proteinases with IC50 of approximately 1 microM. This compound showed a high degree of selectivity in that it did not inhibit cathepsin D and renin.
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PMID:Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitor. 219 May 54

Splenopentin (SP-5: Arg-Lys-Glu-Val-Tyr), a pentapeptide corresponding to the residues 32-36 of the splenic hormone splenin, increases dose-dependently the number of bone marrow colonies (M and GM colonies). Therefore, we tested the stimulatory effect of SP-5 on the recruitment of epidermal Langerhans cells in skin deprived of these cells. A high dose of cyclophosphamide or dexamethasone led to a drastic decrease of LC density in murine skin with slow and incomplete restoration. SP-5 accelerated Langerhans cell recruitment and led to pretreatment levels of Langerhans cell density in the skin. These results indicate that SP-5 may possibly be used to treat disorders (e.g., HIV infection) where impaired Langerhans cell density and function can lead to secondary cutaneous infections.
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PMID:Stimulation of the recruitment of epidermal Langerhans cells by splenopentin. 232 10

The tat gene of HIV-1 is a potent trans-activator of gene expression from the HIV long terminal repeat (LTR). To define the functionally important regions of the product of the tat gene (Tat) of HIV-1, deletion, linker insertion and single amino acid substitution mutants within the Tat coding region of strain SF2 were constructed. The effect of these mutations on trans-activation was assessed by measuring the expression of the bacterial chloramphenicol acetyltransferase (CAT) reporter gene linked to the HIV-LTR. These studies have revealed that four different domains of the protein that map within the N-terminal 56 amino acid region are essential for Tat function. In addition to the essential domains, an auxiliary domain that enhances the activity of the essential region has also been mapped between amino acid residues 58 and 66. One of the essential domains maps in the N-terminal 20 amino acid region. The other three essential domains are highly conserved among the various strains of HIV-1 and HIV-2 as well as simian immunodeficiency virus (SIV). Of the conserved domains, one contains seven Cys residues and single amino acid substitutions for several Cys residues indicate that they are essential for Tat function. The second conserved domain contains a Lys X Leu Gly Ile X Tyr motif in which the Lys residue is essential for trans-activation and the other residues are partially essential. The third conserved domain is strongly basic and appears to play a dual role. Mutants lacking this domain are deficient in trans-activation and in efficient targeting of Tat to the nucleus and nucleolus. The combination of the four essential domains and the auxiliary domain contribute to the near full activity observed with the 101 amino acid Tat protein.
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PMID:Multiple functional domains of Tat, the trans-activator of HIV-1, defined by mutational analysis. 254 2

Protein myristoylation was first discovered in the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase. Subsequently, various cellular and viral myristoylated proteins were detected. In each case, the myristoyl moiety was found in an amide linkage with the amino terminal glycine residue of the modified proteins. The biological functions of protein myristoylation of various cellular protein, oncogene product, and viral structural proteins have been studied by many biochemists. Two of the most thoroughly studies myristoylated proteins are the transforming protein of Rous sarcoma virus, pp60v-src, and the proto-oncogene product, pp60c-src. Deletion, modification of the first 14 NH2-terminal amino acid of pp60v-src, or chemical antimyristoylation of the protein with N-myristoyl glycinal diethylacetal does not affect intrinsic tyrosine src-kinase activity, but prevents myristoylation and membrane association, and abolishes the transforming activity of the protein. Protein myristoylations of some viral structural proteins were also studied by many investigators, and X-ray crystallographic studies of poliovirus suggest that myristate moiety may play a central role in capsid assembly. Recently, human immunodeficiency virus, HIV-I, process a myristoylated p17gag protein, which is proteolytically derived from the NH2-terminus of a gag precursor protein, and its myristate moiety may be important for virus assembly. In this review, we detailed recent studies of the protein myristoylation in cellular regulation and virus proliferation.
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PMID:[Function of protein myristoylation in cellular regulation and viral proliferation]. 254 55

The cyclo [Thr-Thr-Thr-Tyr-Asn-Thr] hexapeptide related to peptide T, H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, competitor of the Human Immunodeficiency Virus in the binding to human T cells, was synthesized and tested for its ability to stimulate monocyte migration (chemotaxis). The new cyclic derivative showed negligible biological activity.
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PMID:Synthesis and biological activity of a cyclic hexapeptide related to peptide T. 263 9

The synthetic peptide of sequence H-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-OH, termed peptide T, a competitor of the Human Immunodeficiency Virus in the binding to human T cells, and its C-terminal pentapeptide fragment, were studied by 1H-nmr in DMSO solution to determine conformational preferences. The observation of nuclear Overhauser enhancements (NOEs) for both peptides, and unusual finding for small linear peptides, allowed complete sequence-specific resonance assignments. Long-range NOEs, ring-current shifts, and the very small temperature coefficient of the Thr8 NH chemical shift suggest, for the zwitterionic form of peptide T, the presence in solution of a beta-turn involving Thr5, Asn6, Tyr7 and Thr8. This conformational feature is consistent with previous structure-activity relationship studies indicating the invariance of the same residues in several potent pentapeptide analogues. The studied pentapeptide fragment, although less structured, shows some tendency to fold even in a polar solvent such as DMSO. Preliminary chemotaxis data on some pentapeptide analogues are consistent with our structural model.
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PMID:Conformational analysis of peptide T and of its C-pentapeptide fragment. 272 Jan 20

A 16-residue synthetic peptide corresponding to the N-terminal sequence of p60src was used as the acyl acceptor in an assay for myristoyl-CoA:glycylpeptide N-myristoyltransferase in rat tissues. An additional C-terminal tyrosine amide was added to this peptide to facilitate radioiodination and enhance detectability. Reverse-phase h.p.l.c. enabled the simultaneous detection and quantification of the peptide substrate and its N-myristoylated product. N-Myristoyltransferase activity was highest in the brain with decreasing activities in lung, small intestine, kidney, heart, skeletal muscle and liver. Brain activity was distributed approximately equally between the 100,000 g pellet and supernatant fractions. The soluble enzyme exhibited a Kappm of 20 microM for the src peptide and an optimum between pH 7.0 and 7.5. Maximum N-acylating activity was seen with myristoyl (C14:0)-CoA with lower activities found with the C10:0-CoA and C12:0-CoA homologues. No activity was obtained with palmitoyl (C18:0)-CoA but this derivative inhibited N-myristoyltransferase activity greater than 50% at equimolar concentrations with myristoyl-CoA. With a decapeptide corresponding to the N-terminal sequence of the cyclic AMP-dependent protein kinase catalytic subunit as the acyl acceptor, the brain enzyme displayed a Kapp.m of 117 microM and was about 14-fold less catalytically effective than with the p60src acyl acceptor. Transferase activity was also seen with a 16-residue peptide corresponding to the N-terminal sequence of the HIV p17gag structural protein. Inhibition studies with shorter src peptide analogues indicated an enzyme specificity for the p60src acyl acceptor beyond 9 residues.
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PMID:N-myristoylation of p60src. Identification of a myristoyl-CoA:glycylpeptide N-myristoyltransferase in rat tissues. 312 85

An antibody detection procedure based on agglutination of autologous red cells has been developed for samples of whole blood. A nonagglutinating monoclonal antibody to human red blood cells conjugated to a synthetic peptide antigen (in this case residues 579 to 601 of the HIV-1 envelope precursor, Arg-Ile-Leu-Ala-Val-Glu-Arg-Tyr-Leu-Lys-Asp-Gln-Gln-Leu-Leu-Gly-Ile-Trp- Gly-Cys - Ser-Gly-Lys) permitted the detection of antibodies to the human immunodeficiency virus type 1 (HIV-1) in 10 microliters of whole blood within 2 minutes. Agglutination was specifically inhibited by addition of synthetic peptide antigen but not by unrelated peptides. The frequency of false positive results was 0.1% with HIV-1 seronegative blood donors (n = 874). The false negative results were approximately 1% (n = 81). The autologous red cell agglutination test is potentially suitable for simple, rapid, qualitative screening for antibodies to a variety of antigens of medical and veterinary diagnostic significance.
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PMID:Autologous red cell agglutination assay for HIV-1 antibodies: simplified test with whole blood. 341 97

The Vpr accessory gene product of human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus is believed to play a role in permitting entry of the viral core into the nucleus of nondividing cells. A second role for Vpr was recently suggested by Rogel et al. (M. E. Rogel, L. I. Wu, and M. Emerman, J. Virol. 69:882-888, 1995), who showed that Vpr prevents the establishment in vitro of chronically infected HIV producer cell lines, apparently by causing infected cells to arrest in the G2/M phase of the cell cycle. In cycling cells, progression from G2 to M phase is driven by activation of the p34cdc2/cyclin B complex, an event caused, in part, by dephosphorylation of two regulatory amino acids of p34cdc2 (Thr-14 and Tyr-15). We show here that Vpr arrests the cell cycle in G2 by preventing the activation of the p34cdc2/cyclin B complex. Vpr expression in cells caused p34cdc2 to remain in the phosphorylated, inactive state, p34cdc2/cyclin B complexes immunoprecipitated from cells expressing Vpr were almost completely inactive in a histone H1 kinase assay. Coexpression of a constitutively active mutant p34cdc2 molecule with Vpr relieved the G2 arrest. These findings strongly suggest that Vpr arrests cells in G2 by preventing the activation of the p34cdc2/cyclin B complex that is required for entry into M phase. In vivo, Vpr might, by preventing p34cdc2 activation, delay or prevent apoptosis of infected cells. This would increase the amount of virus each infected cell produced.
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PMID:Human immunodeficiency virus type 1 viral protein R (Vpr) arrests cells in the G2 phase of the cell cycle by inhibiting p34cdc2 activity. 747 80

HIV-1 strains were isolated from four patients treated with AZT for more than 6 months and from three patients untreated with AZT. Isolates from patients treated with AZT have been cultured by passage of virus in cell culture in the presence of 1 microM AZT. However the isolates from patients untreated with AZT could not be cultured in the presence of AZT. The RT gene of HIV-1 isolates which had been cultured in the presence of AZT were amplified by PCR and cloned to M13 vector. Four amino acid mutations in RT gene (Asp67, Lys70, Thr215, Lys219) associated with resistance to AZT were analysed. All of the 22 clones obtained from the isolates in the presence of 1 microM AZT had mutations at codon 215(Thr-->Tyr or Phe). Some of the 22 clones also had other mutations at codon 67 (Asp-->Ser), codon 70 (Lys-->Arg) and codon 219 (Lys-->Glu or Gln). Four amino acid residues in RT gene of the isolates which had been cultured in the presence of AZT were compared to that of the isolates cultured in the absence of AZT. The clones of the isolates obtained from the patients (04 or 05) had mutations at only codon 215 Thr-->Tyr) in both the presence and the absence of AZT. All of the clones of the isolates obtained from the patients (06 or 07) had mutations at codon 215 and some of them had other mutations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Reverse transcriptase gene analysis of HIV-1 mutants cultured in the presence of AZT]. 750 15


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