Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A synthetic peptide (SP-10-IIIB) with an amino acid sequence [Cys-Thr-Arg-Pro-Asn-Asn-Asn-Thr-Arg-Lys-Ser-Ile-Arg-Ile-Gln-Arg-Gly-Pro -Pro-Gly-(Tyr); amino acids 303-321] from the human immunodeficiency virus (HIV) isolate human T-cell lymphotropic virus type III (HTLV-III) HTLV-IIIB envelope glycoprotein gp120 was coupled to tetanus toxoid and used to raise goat antibodies to HIV gp120. Goat anti-SP-10-IIIB serum bound to the surface of HTLV-IIIB-infected CEM T cells but not to the surface of HTLV-IIIRF-infected or uninfected CEM T cells. Anti-SP-10-IIIB antibodies also selectively bound to gp120 from lysates of HTLV-IIIB cells in immunoblot assays. Twenty-one percent of sera (28 of 175) from patients seropositive for HIV contained antibodies that reacted with SP-10-IIIB in RIA. Human anti-SP-10-IIIB antibodies affinity purified from acquired immunodeficiency syndrome (AIDS) patient serum bound to HTLV-IIIB-infected cells and immunoprecipitated gp120. Goat antibodies to SP-10-IIIB neutralized HTLV-IIIB (80% neutralization titer of 1/600), inhibited HTLV-IIIB-induced syncytium formation, but did not neutralize HIV isolates HTLV-IIIRF or HTLV-IIIMN or inhibit syncytium formation with these isolates. Also, goat antiserum to an homologous synthetic peptide [SP-10-IIIRF(A), (Cys)-Arg-Lys-Ser-Ile-Thr-Lys-Gly-Pro-Gly-Arg-Val-Ile-Tyr] from gp120 of HIV isolate HTLV-IIIRF inhibited syncytium formation by HTLV-IIIRF, but did not inhibit syncytium formation by HTLV-IIIB or by HTLV-IIIMN. Thus, the amino acid sequences of SP-10-IIIB and SP-10-IIIRF(A) define homologous regions of gp120 that are important in type-specific virus neutralization. The identification of these type-specific neutralizing epitopes should facilitate the design of a polyvalent, synthetic vaccine for AIDS.
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PMID:Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. 245 Mar 51

Earlier work from this and other laboratories has revealed the presence within Mycobacterium spp. of three classes of glycolipid antigens which we have called the glycopeptidolipids, the lipooligosaccharides and the phenolic glycolipids. Representative structures of each from different species and sub-species have been proposed. More recently, new variants of these antigens and older structures have been analyzed by Fourier transform infrared, NMR, particularly at high temperatures, and, most notably, by fast atom bombardment and Californium desorption mass spectrometry. Extraordinary novelty and diversity were revealed, particularly at the distal non-reducing end of the oligosaccharide chains, marked by the presence of new branched-chain sugars, amino sugars and sugar acids. These epitopes and monoclonal antibodies to them have been used for the critical identification of mycobacteria. In addition, the pure antigens are the basis of specific serological tests for various mycobacterioses. The resurgence of interest in "atypical" mycobacteria stems from their occurrence as opportunistic pathogens in many patients with acquired immunodeficiency syndrome, although they have long been associated with pulmonary and other organ infections. Foremost among these mycobacteria are serovars of the Mycobacterium avium-Mycobacterium intracellulare complex (the M. avium complex). The surface antigens which differentiate these serovars are glycopeptidolipids, related to "mycoside C" and, accordingly, composed of a glycosylated lipopeptide "core", fatty acyl-D-Phe-D-alloThr-D-Ala-L-acanyl-O- (3,4-di-O-methyl-alpha-L-rhamnopyranoside), to which a haptenic oligosaccharide is linked at the threonine substituent; this oligoglycosyl unit is the source of type specificity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Structure and function of mycobacterial glycolipids and glycopeptidolipids. 250 12

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

Oligopeptides containing the consensus retroviral protease cleavage sequence Ser/Thr-X-Y-Tyr/Phe-Pro are substrates for purified recombinant HIV-1 protease with Km's in the millimolar range. The minimum sequence containing the consensus pentapeptide which serves as a good substrate is a heptapeptide spanning the P4-P3' residues. Substitution of reduced Phe-Pro or Tyr-Pro dipeptide isosteres or the statine analog 3-hydroxy-4-amino-5-phenylpentanoic acid for the scissile dipeptide afforded inhibitors of HIV-1 protease with Ki values in the micromolar range, three orders of magnitude better in affinity than the corresponding substrates. Inhibitors of HIV-1 protease may provide a novel and potentially useful therapeutic approach to the treatment of acquired immune deficiency syndrome (AIDS).
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PMID:Peptide substrates and inhibitors of the HIV-1 protease. 264 94

Knowledge of the tertiary structure of the proteinase from human immunodeficiency virus HIV-1 is important to the design of inhibitors that might possess antiviral activity and thus be useful in the treatment of AIDS. The conserved Asp-Thr/Ser-Gly sequence in retroviral proteinases suggests that they exist as dimers similar to the ancestor proposed for the pepsins. Although this has been confirmed by X-ray analyses of Rous sarcoma virus and HIV-1 proteinases, these structures have overall folds that are similar to each other only where they are also similar to the pepsins. We now report a further X-ray analysis of a recombinant HIV-1 proteinase at 2.7 A resolution. The polypeptide chain adopts a fold in which the N- and C-terminal strands are organized together in a four-stranded beta-sheet. A helix precedes the single C-terminal strand, as in the Rous sarcoma virus proteinase and also in a synthetic HIV-1 proteinase, in which the cysteines have been replaced by alpha-aminobuytric acid. The structure reported here provides an explanation for the amino acid invariance amongst retroviral proteinases, but differs from that reported earlier in some residues that are candidates for substrate interactions at P3, and in the mode of intramolecular cleavage during processing of the polyprotein.
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PMID:X-ray analysis of HIV-1 proteinase at 2.7 A resolution confirms structural homology among retroviral enzymes. 268 66

The conditioned medium of a HTLV-I-carrying T cell line HUT-102 showed cytotoxic activity against a mouse fibroblast cell line L-M. We prepared the cDNA library from HUT-102 poly(A)+ RNA and screened it using oligonucleotide probes that correspond to the amino acid sequences conserved in tumor necrosis factor (TNF) and lymphotoxin (LT). As a result we obtained two kinds of cDNA clones encoding LT in which amino acid residue 26t of mature LT is different; one is Asn and another is Thr. The sequence of the genomic clones obtained using a polymerase chain reaction method showed that the HUT-102 genome also contains two types of LT genes. Recombinant LTs expressed in Escherichia coli exhibited the same level of cytolytic activity against L-M cells. These results indicate that the cytotoxin constitutively produced by HUT-102 cells include two kinds of LT.
AIDS Res Hum Retroviruses 1989 Dec
PMID:Lymphotoxin cDNA clones from a HTLV-I-carrying T cell line HUT-102. 269 60

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 recently proposed octapeptide, [D-Ala]peptide T amide (D-Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr-NH2), has been shown to bind to the CD4 receptor on human T-cell lymphocytes and block human immunodeficiency viral infectivity. This peptide may not only be itself a promising therapeutic for the disease of AIDS (acquired immune deficiency syndrome), but might open a new avenue of research towards more efficacious drugs. Accordingly, a counter-current chromatography system is here presented, utilizing the Ito flow-through coil planet centrifuge (solvent system, 1% trifluoroacetic acid-n-butanol (1:1), upper phase mobile) which allows facile preparative purification of [D-Ala]peptide T amide. The method may be applicable to purifying analogues of [D-Ala]peptide T amide as they are developed.
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PMID:Counter-current chromatographic purification of [D-Ala]peptide T amide. 344 32

c-Myc is a helix-loop leucine zipper phosphoprotein that heterodimerizes with Max and regulates gene transcription in cell proliferation, cell differentiation, and programmed cell death. Previously, we demonstrated that c-Myc is modified by O-linked N-acetylglucosamine (O-GlcNAc) within or nearby the N-terminal transcriptional activation domain (Chou, T.-Y., Dang, C.V., and Hart, G.W. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 4417-4421). In this paper, we identified the O-GlcNAc attachment site(s) on c-Myc. c-Myc purified from sf9 insect cells was trypsinized, and its GlcNAc moieties were enzymically labeled with [3H]galactose. The [3H]galactose-labeled glycopeptides were isolated by reverse phase high performance liquid chromatography and then subjected to gas-phase sequencing, manual Edman degradation, and laser desorption/ionization mass spectrometry. These analyses show that threonine 58, an in vivo phosphorylation site in the transactivation domain, is the major O-GlcNAc glycosylation site of c-Myc. Mutation of threonine 58, frequently found in retroviral v-Myc proteins and in human Burkitt and AIDS-related lymphomas, is associated with enhanced transforming activity and tumorigenicity. The reciprocal glycosylation and phosphorylation at this biologically significant amino acid residue may play an important role in the regulation of the functions of c-Myc.
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PMID:c-Myc is glycosylated at threonine 58, a known phosphorylation site and a mutational hot spot in lymphomas. 764 55

O-linked N-acetylglucosamine (O-GlcNAc) is an abundant and dynamic posttranslational modification composed of a single monosaccharide, GlcNAc, glycosidically composed of a single monosaccharide, GlcNAc, glycosidically linked to the side-chain hydroxyl of serine or threonine residues. Although O-GlcNAc occurs on a myriad of nuclear and cytoplasmic proteins, only a few have thus far been identified. These O-GlcNAc-bearing proteins are also modified by phosphorylation and form reversible multimeric complexes. Here we present evidence for O-GlcNAc glycosylation of the oncoprotein c-Myc, a helix-loop-helix/leucine zipper phosphoprotein that heterodimerizes with Max and participates in the regulation of gene transcription in normal and neoplastic cells. O-GlcNAc modification of c-Myc is shown by three different methods: (i) demonstration of lectin binding to in vitro translated protein using a protein-protein interaction mobility-shift assay; (ii) glycosidase or glycosyltransferase treatment of in vitro translated protein analyzed by lectin affinity chromatography; and (iii) direct characterization of the sugar moieties on purified recombinant protein overexpressed in either insect cells or Chinese hamster ovary cells. Analyses of serial deletion mutants of c-Myc further suggest that the O-GlcNAc site(s) are located within or near the N-terminal transcription activation/malignant transformation domain, a region where mutations of c-Myc that are frequently found in Burkitt and AIDS-related lymphomas cluster.
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PMID:Glycosylation of the c-Myc transactivation domain. 775 21


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