Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Human immunodeficiency virus type 1 (HIV-1) strain LAV-1 (HIV-1(LAV-1)) particles were collected by ultracentrifugation, treated with subtilisin, and then purified by Sepharose CL-4B column chromatography to remove microvesicles. The lysate of the purified HIV-1(LAV-1) particles was subjected to two-dimensional (2D) gel electrophoresis and stained. The 2D gel electrophoresis image suggested that 24 proteins can be identified inside the virion. Furthermore, the stained protein spots were excised and digested with trypsin. The resulting peptide fragments were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Peptide mass fingerprinting data suggested that two isoforms of cyclophilin A (CyPA), one with an isoelectric point (pI) of 6.40 and one with a pI of 6.53, are inside the viral membrane; that another isoform, with a pI of 6.88, is outside the viral membrane; and that the CyPA isoform with a pI of 6.53 is N acetylated. The mechanisms that permit the redistribution of CyPA on the viral surface have not yet been clarified, but it is surmised that the CyPA isoform with a pI of 6.88 may play a critical role in the attachment of virions to the surface of target cells and that both CyPA isoforms with pIs of 6.40 and 6.53 may regulate the conformation of the HIV-1 capsid protein.
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PMID:Three isoforms of cyclophilin A associated with human immunodeficiency virus type 1 were found by proteomics by using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry. 1220 76

An antigenic peptide analogue consisting of HIV gp120 residues 421-431 (an antigen recognition site probe) with diphenyl amino(4-amidinophenyl)methanephosphonate located at the C-terminus (a catalytic site probe) was synthesized and its trypsin and antibody reactivity characteristics were studied. Antibodies to the peptide determinant recognized the peptidyl phosphonate probe. Trypsin was inhibited equipotently by the peptidyl phosphonate and its simple phosphonate counterpart devoid of the peptide determinant. The peptidyl phosphonate inhibited the gp120-hydrolyzing activity of a catalytic antibody light chain. It was bound covalently by the light chain and the binding was inhibited by the classical active-site directed inhibitor of serine proteinase, diisopropyl fluorophosphate. These results reveal that the peptidyl phosphonate ester can serve as a probe for the antigen recognition and catalytic subsites of proteolytic antibodies.
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PMID:A mechanism-based probe for gp120-Hydrolyzing antibodies. 1237 25

Pastor and Cruciani [J. Med. Chem. 38 (1995) 4637] and Kastenholz et al. [J. Med. Chem. 43 (2000) 3033] pioneered methods for comparing related receptors, with the ultimate goal of designing selective ligands. Such methods start with a reasonable superposition of high-resolution three-dimensional (3D) structures of the receptors. Next, molecular field maps are calculated for each receptor. Then the maps are analyzed to determine which map features are correlated with a particular subset of receptors. We present a method FLOGTV, based on the trend vector paradigm [J. Chem. Inf. Comput. Sci. 25 (1985) 64] to perform the analysis. This is mathematically simpler than the GRID/CPCA method of Kastenholz et al. and allows for the simultaneous comparison of many receptor structures. Also, the trend vector paradigm provides a method of selecting isopotential contours that are well above "noise". We demonstrate the method on four examples: HIV proteases versus two-domain acid proteases, thrombin versus trypsin and factor Xa, bacterial dihydrofolate reductases (DHFRs) versus vertebrate DHFRs, and P38 versus ERK protein kinases.
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PMID:A simple method for visualizing the differences between related receptor sites. 1246 40

A coupled transcription-translation (TNT) reticulocyte lysate system was used to examine posttranslational alterations in HIV-1 Gag upon addition of Jurkat T cell membranes. Incubation of the Gag precursor protein, Pr55gag, with membranes resulted in a time-dependent alteration in Gag resulting in partial resistance to trypsin treatment. Treatment of membranes and TNT extract with apyrase or pretreatment of membranes with trypsin prevented this posttranslational alteration of Gag. In contrast, this activity was not disrupted by pretreatment of membranes with Triton X-100 at 4 degrees C, under conditions which do not solubilize raft-associated proteins. Flotation studies revealed that acquisition of trypsin-resistance was accompanied by Gag binding to membranes. The myristylation signal and nucleocapsid domain were found to mediate Gag binding to membranes. The posttranslational alteration of Gag accompanying membrane interaction may represent a conformational change, oligomerization, and/or association with or envelopment by membranes. These findings provide new clues to the stepwise process of HIV-1 assembly.
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PMID:Interaction of HIV-1 gag and membranes in a cell-free system. 1242 25

Pastor and Cruciani [J. Med. Chem. 38 (1995) 4637] and Kastenholz et al. [J. Med. Chem. 43 (2000) 3033] pioneered methods for comparing related receptors, with the ultimate goal of designing selective ligands. Such methods start with a reasonable superposition of high-resolution three-dimensional (3D) structures of the receptors. Next, molecular field maps are calculated for each receptor. Then the maps are analyzed to determine which map features are correlated with a particular subset of receptors. We present a method FLOGTV, based on the trend vector paradigm [J. Chem. Inf. Comput. Sci. 25 (1985) 64] to perform the analysis. This is mathematically simpler than the GRID/CPCA method of Kastenholz et al. and allows for the simultaneous comparison of many receptor structures. Also, the trend vector paradigm provides a method of selecting isopotential contours that are well above "noise". We demonstrate the method on four examples: HIV proteases versus two-domain acid proteases, thrombin versus trypsin and factor Xa, bacterial dihydrofolate reductases (DHFRs) versus vertebrate DHFRs, and P38 versus ERK protein kinases.
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PMID:A simple method for visualizing the differences between related receptor sites. 1241 33

A protein with an N-terminal sequence showing a much lesser extent of homology than French bean and kiwi fruit thaumatin-like proteins (TLPs) to other TLPs, and possessing a molecular mass of 30 kDa which is considerably higher than those of previously reported TLPs, has been purified from the seeds of the chestnut Castanopsis chinensis Hance. The protein was unadsorbed on DEAE-cellulose in 10 mM Tris-HCl buffer (pH 7.3), and adsorbed on Affi-gel blue gel in the same buffer, on CM-cellulose in 10 mM ammonium acetate buffer (pH 4.5), and on Mono S in 20 mM ammonium acetate buffer (pH 5.5). A highly purified protein preparation was obtained after fractionation on the first three chromatographic media. Castanopsis TLP appeared as a single band (30 kDa) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and as a single peak (30 kDa) in gel filtration on Superdex 75 by fast protein liquid chromatography. The TLP exerted antifungal activity against Botrytis cinerea, Fusarium oxysporum, Mycosphaerella arachidicola, and Physalospora piricola, with an IC(50) of 0.5 microM against F. oxysporum. Castanopsis TLP was more potent than French bean and kiwi fruit TLPs in its antifungal activity toward F. oxysporum and M. arachidicola. The antifungal activity of Castanopsis TLP remained essentially unaltered after incubation at 40 degrees C for 10 min, was reduced after incubation at 60 degrees C, and disappeared after treatment at 80 degrees C. The antifungal activity underwent a decline after treatment with trypsin (enzyme:substrate ratio 1:100) at 37 degrees C for 1h but some activity remained. Castanopsis TLP exhibited a much more potent inhibitory activity on HIV-1 reverse transcriptase (IC(50) = 1.6 microM) than kiwi fruit TLP (IC(50) > or = 27 microM). Castanopsis TLP was obtained with a yield of 20 mg from 1 kg chestnut seeds.
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PMID:Isolation of a large thaumatin-like antifungal protein from seeds of the Kweilin chestnut Castanopsis chinensis. 1256 69

An association between human immunodeficiency virus type I (HIV-1) protease inhibitors (PIs) and galactorrhoea/hyperprolactinemia adverse effect has recently been reported in four HIV-1-infected women treated with PIs (indinavir, nelfinavir, ritonavir or saquinavir). This could be explained by a direct effect of ritonavir and saquinavir on anterior pituitary prolactin (PRL) release, and/or an indirect effect of PIs on the secretion of hypothalamic dopamine, which is the main PRL inhibitory factor. Anterior pituitaries were explanted from adult male Wistar rats, the cells were trypsin dispersed, plated into multiwell cultures and incubated for 1 h with either ritonavir or saquinavir (0.01 nM-1μM). PRL release into the incubation medium was evaluated by radioimmunoassay. Hypothalamic neuronal endings (synaptosomes) were prepared by tissue homogenization, incubated with ³H-dopamine, substituting for the endogenous dopamine pool, and perfused with ritonavir or saquinavir, both basally and during depolarization (K⁺ 15 mM)-induced dopamine release. Beta-emission from 2 min perfusate fractions, corresponding to ³H-dopamine release, was detected by liquid scintillation scanning. We found that both ritonavir and saquinavir are able to significantly stimulate PRL secretion, with saquinavir slightly more effective than ritonavir. On the contrary, both protease inhibitors do not modify either basal or depolarization-induced dopamine release. We can speculate that HIV PIs despite a high affinity for the catalytic site of HIV protease, could also bind to and inhibit homologous mammalian proteins in the anterior pituitary that are involved in PRL secretion.
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PMID:Ritonavir and Saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro. 1259 90

A homodimeric trypsin inhibitor with a molecular mass of 54 kDa was isolated from the seeds of Clausena lansium (Lour) Skeels with a very simple procedure comprising extraction with an aqueous buffer and ion exchange chromatography on CM-cellulose. It inhibited trypsin with an IC50 of 2.2 nM but was without any inhibitory effect on chymotrypsin and proteinase K. The uptake of MTT by human leukemia HL60 and hepatoma Hep G2 cells was inhibited with an IC50 of 100 microM. Translation in the cell-free rabbit reticulocyte lysate system was inhibited with an IC50 of 3.6 microM. The activity of HIV-1 reverse transcriptase was reduced in the presence of the trypsin inhibitor. The trypsin inhibitor exerted antifungal activity toward Physalospora piricola but not Mycosphaerella arachidicola, Botrytis cinerea, Fusarium oxysporum or Coprinus comatus.
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PMID:A homodimeric sporamin-type trypsin inhibitor with antiproliferative, HIV reverse transcriptase-inhibitory and antifungal activities from wampee (Clausena lansium) seeds. 1267 22

A series of new 7-substituted-4-chloro-3-alkoxy isocoumarin derivatives were synthesized and evaluated as inhibitors of representative classes of proteases: serine protease (alpha-chymotrypsin, trypsin), cysteine protease (Caspase-3), and aspartyl protease (HIV-protease), 20S proteasome and also as inhibitors of amyloid peptide gamma-secretase-mediated production. Protease inhibition selectivity is directly related to the structure of the substituent at the 7-position of the isocoumarin nucleus. 7-Nitro-isocoumarin derivatives (4c, 4d, 4f) are potent alpha-chymotrypsin inhibitors but slightly active or inactive on HIV-protease, as well as on cysteine protease. In contrast, only derivatives bearing a free amino (5d, 5f) or a substituted amino group (6f) at the 7-position of the isocoumarin nucleus, were found weakly active or inactive on alpha-chymotrypsin, trypsin, Caspase-3 and HIV-protease, but prevent gamma-secretase-mediated production of Abeta 40/42 amyloid peptides, which is known to be involved in Alzheimer's disease. Moreover, the most active compounds on beta-amyloid peptide production [JLK6 (5d), JLK2 (5f) and JLK7 (6f)] show only weak or moderate inhibitory activity on the 20S proteasome. The obtained results suggest that the described new isocoumarin analogues could be of interest, since compounds like JLK6 (5d), JLK2 (5f) and JLK7 (6f) can be considered as possible hits for the development of new agents directed towards Alzheimer's disease.
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PMID:Synthesis of new 3-alkoxy-7-amino-4-chloro-isocoumarin derivatives as new beta-amyloid peptide production inhibitors and their activities on various classes of protease. 1281 77

Interactions of human immunodeficiency virus type 1 (HIV-1) with immature dendritic cells (DC) are believed to be multifactorial and involve binding to the CD4 antigen, DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), mannose binding C-type lectin receptors (MCLR), and heparan sulfate proteoglycans (HSPG). In this study we assessed the relative contributions of these previously defined virus attachment factors to HIV binding and accumulation in DC and the subsequent transfer of the bound virus particle to CD4(+) T cells. Using competitive inhibitors of HIV-1 attachment to DC, we have identified the existence of DC-SIGN-, MCLR-, and HSPG-independent mechanism(s) of HIV attachment and internalization. Furthermore, virus particles bound by DC independently of CD4, DC-SIGN, MCLR, and HSPG are efficiently transmitted to T cells. Treatment of virus particles with the protease subtilisin or treatment of immature DC with trypsin significantly reduced virus binding, thus demonstrating the role of HIV envelope glycoprotein interactions with unidentified DC-surface factor(s). Finally, this DC-mediated virus binding and internalization are dependent on lipid rafts. We propose that pathways to HIV-1 attachment and uptake in DC exhibit functional redundancy; that is, they are made up of multiple independent activities that can, at least in part, compensate for one another.
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PMID:Binding of human immunodeficiency virus type 1 to immature dendritic cells can occur independently of DC-SIGN and mannose binding C-type lectin receptors via a cholesterol-dependent pathway. 1461 Feb 7


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