UMLS:C0021051 - FACTA Search

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

Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two-dimensional NMR, circular dichroism (CD) experiments and molecular modeling were performed to study the secondary structure of a 44-mer peptide fragment derived from the C4 region of gp120 of human immunodeficiency virus in aqueous solution. It was found a nascent helical structure exists following a type I turn near the N-terminus of the peptide. The proline residue in the turn appears to serve as a helix initiator. The helical structure was in fast dynamic equilibrium with beta- or random coil form on the NMR scale. A reverse turn was identified at a section containing two consecutive proline residues. A nascent helical structure has been detected for the region near the C-terminus of the 44-mer peptide. Higher helical content for the peptide is also indicated by CD studies on TFE titration. Thus it is proposed that, in more apolar medium, the Pro-Pro turn and the segment amino-terminal to it, spanning about 20 amino acids, may be converted into helix structure. Moreover, the region near the C-terminus of the peptide may also be induced into helix, so that a helix-turn-helix structure may be formed in the C4 domain of gp120. A helical wheel representation of this stretch shows amphipathicity of the helix. The biological implication of the conformational adaptibility of the peptide was discussed.
...
PMID:NMR and circular dichroism studies on the conformation of a 44-mer peptide from a CD4-binding domain of human immunodeficiency virus envelope glycoprotein. 921 Dec 25

Antisense phosphorothioate oligodeoxyribonucleotides (PS oligonucleotides) have the ability to inhibit individual gene expression in the potential treatment of cancer and viral diseases. Following administration in vivo, PS oligonucleotides are rapidly cleared from the plasma and distributed to various organs. However, the manner in which administered oligonucleotides are metabolized in plasma and tissues is poorly understood. In this study, a 25-mer PS oligonucleotide (GEM91) complementary to the gag gene mRNA of the human immunodeficiency virus (HIV-1) was administered to mice through intravenous injections to investigate its metabolism. The PS oligonucleotide was extracted from plasma at 1 hour postadministration and from kidney and liver at 24 hours postadministration. After extraction, the PS oligonucleotide and its metabolites were tailed with dA and annealed to a dT-tailed plasmid. The recombinant plasmid was ligated and used to transform competent bacteria. The region of interest containing the PS oligonucleotide was then sequenced. Our results show that degradation of the PS oligonucleotide in plasma was primarily from the 3'-end. However, in kidney and liver, degradation was primarily from the 3'-end, but a large proportion of the PS oligonucleotide was degraded from the 5'-end as well. We also studied the metabolism of PS oligonucleotide in plasma after 2-hour intravenous infusion in HIV-infected patients. The degradation of the PS oligonucleotide in plasma was primarily from the 3'-end. This study is important in understanding the metabolism of antisense PS oligonucleotide in vivo in general but also provides guidance for designing second-generation antisense oligonucleotides with improved stability and safety profile.
...
PMID:In vivo metabolic profile of a phosphorothioate oligodeoxyribonucleotide. 921 6

Identification of in vitro immunogenic T-cell epitopes is important for the design of immunotherapeutics targeted to specific antigenic sites. To identify candidate cytotoxic T-lymphocyte (CTL) epitopes in the protease of human immunodeficiency virus type 1 (HIV-1) strain MN, we synthesized 9-mer and 10-mer peptides containing the HLA-A*0201 binding motif. Binding affinity of the peptides was measured by HLA-A*0201 up-regulation on T2 cells. Peptides with high binding-affinity were tested for their ability to stimulate primary CTLs from healthy HIV-negative blood donors. Peptide-specific CTLs were obtained from five out of six donors by stimulation with a 9-mer (LVGPTPVNI) or a 10-mer (VLVGPTPVNI) peptide derived from a highly conserved amino acid stretch in the C-terminal region of the protease. Addition of peptide-specific CTLs to acutely HIV-infected lymphocytes resulted in inhibition of p24gag production. In conclusion, a highly conserved HIV protease peptide regularly elicits peptide-specific CTLs. Targeting immune responses against defined epitopes in non-variable regions may be a feasible way to minimize the risk of virus escape from immune surveillance.
...
PMID:Primary induction of human cytotoxic lymphocytes against a synthetic peptide of the human immunodeficiency virus type 1 protease. 929 9

It has been proposed that the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope gp120 carboxy-terminal sequence, TKAKRRVVEREKR (CT120), may represent a functional mimic of the human leukocyte antigen (HLA) class II DR beta-chain third hypervariable region (HVR3) sequence motif located at position 69-81. Presentation of this potentially pathogenic fragment by HLA class I and/or II molecules, in a manner analogous to the indirect pathway of allorecognition, may induce both widespread cellular activation and also break self-tolerance, resulting in the selective and progressive anti-self HLA class II-directed immune suppression, which is a central feature of HIV-1 infection and the associated acquired immune deficiency syndrome (AIDS). To investigate the functional role of the HIV-1 gp120 C-terminal fragment T cell lines (TCLs) were raised from three healthy HIV-1-seronegative subjects at low risk of HIV-1 exposure, by repeated stimulation with a short synthetic 13-mer CT120 peptide in vitro. Graded concentrations (10[3] to 5 x 10[4]) of CT120 TCLs suppressed the primary 6-day proliferation of autologous PBMCs in response to the soluble antigens tetanus toxoid (TT) and purified protein derivative (PPD). In contrast, CT120 TCLs demonstrated no suppressive effect on 3-day phytohemagglutinin (PHA), concanavalin A (ConA), and pokeweed mitogen (PWM) mitogenic responses. Fractionation of CT120 TCLs into highly purified CD4+ and CD8+ T cell subsets demonstrated that the CD8+ T cell fraction mediated the suppressor effector function. HLA restriction analysis revealed a complex pattern as both anti-HLA class II DR and anti-HLA class I (A, B, C) MAbs inhibited proliferation of oligoclonal CD8+ CT120 TCLs. Strategies aimed at specifically inhibiting such putative immunopathogenic HIV-1-encoded T cell epitopes may be an important consideration for development of future HIV-1 immunotherapy.
...
PMID:HIV type 1 envelope glycoprotein 120 carboxy-terminal peptide-induced human T cell lines selectively suppress heterogeneous proliferative T cell responses to soluble antigens. 933 48

The conformation of the DNA and the interactions of the nucleic acid with the protein in a complex of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and 19-mer/18-mer double-stranded DNA template-primer (dsDNA) are described. The structure of this HIV-1 RT complex with dsDNA serves as a useful paradigm for studying aspects of nucleotide polymerases such as catalysis, fidelity, drug inhibition, and drug resistance. The bound dsDNA has a bend of approximately 41 degrees at the junction of an A-form region (first five base pairs near the polymerase active site) and a B-form region (the last nine base pairs toward the RNase H active site). The 41 degrees bend occurs smoothly over the four base pairs between the A-form portion and the B-form portion in the vicinity of helices alpha H and alpha I of the p66 thumb subdomain. The interactions between the dsDNA and protein primarily involve the sugar-phosphate backbone of the nucleic acid and structural elements of the palm, thumb, and RNase H of p66, and are not sequence specific. Amino acid residues from the polymerase active site region, including amino acid residues of the conserved Tyr-Met-Asp-Asp (YMDD) motif and the "primer grip," interact with 3'-terminal nucleotides of the primer strand and are involved in positioning the primer terminal nucleotide and its 3'-OH group at the polymerase active site. Amino acid residues of the "template grip" have close contacts with the template strand and aid in positioning the template strand near the polymerase active site. Helix alpha H of the p66 thumb is partly inserted into the minor groove of the dsDNA and helix alpha I is directly adjacent to the backbone of the template strand. Amino acid residues of beta 1', alpha A', alpha B', and the loop containing His539 of the RNase H domain interact with the primer strand of the dsDNA.
...
PMID:Protein-nucleic acid interactions and DNA conformation in a complex of human immunodeficiency virus type 1 reverse transcriptase with a double-stranded DNA template-primer. 935 57

Identifying infectious organisms, quantitating gene expression, and sequencing genomic DNA on chips all rely on the detection of nucleic acid hybridization. Described here is a novel assay for detection of the hybridization of products of the polymerase chain reaction using electron transfer from guanine to a transition-metal complex. The hybridization assay was modeled in solution by monitoring the cyclic voltammetry of Ru(bpy)3(2+) (bpy = 2,2'-bipyridine) in the presence of a probe strand containing only A, T, and C prior to and after hybridization to a complement that contained seven guanines, which led to high catalytic current due to the oxidation of guanine by Ru(bpy)3(3+). To allow recognition of all four bases in the target sequence, it was shown that inosine 5'-monophosphate was 3 orders of magnitude less reactive than guanosine 5'-monophosphate, suggesting that effective hybridization sensors could be realized by immobilization of probe strands in which inosine was substituted for guanosine; hybridization to guanosine-containing target strands would then provide high catalytic currents. A sensor design was tested in a model system for the detection of a synthetic 21-mer oligonucleotide patterned on the sequence of the ras oncogene, which gave an increase in charge collected of 35 +/- 5 microC after hybridization and of only 8 +/- 5 microC after exposure to noncomplementary DNA. Independent quantitation of probe and target by radiolabeling showed that the hybridized electrode contained 3.0 +/- 0.3 ng of target. New sensor electrodes were then prepared for the detection of PCR-amplified genomic DNA from herpes simplex virus type II, genomic DNA from Clostridium perfringens, and genomic RNA from human immunodeficiency virus and gave an additional charge of 35-65 microC for hybridization to complementary amplicon and of only 2-10 microC after exposure to noncomplementary DNA.
...
PMID:Probing biomolecule recognition with electron transfer: electrochemical sensors for DNA hybridization. 940 65

The solution conformations of the all L-alpha-peptide 1 and the corresponding retro-all D-alpha-peptide 2, two 20-metric peptides which generate antibodies that cross-react with the gp 120 envelop protein of human immunodeficiency virus-1 (HIV-1), have been investigated by high-field 1H NMR spectroscopy. Complete sequential and inter-residue interaction assignments were made from the 2D NMR spectra acquired at 500 MHz and 600 MHz in 40% deuterotrifluoroethanol (d3-TFE)/H2O at pH 2.3, and in 300 mM sodium dodecyl sulphate (SDS) in 100% D2O or 90% H2O/10% D2O at pH 2.6. Based on analysis of the nuclear Overhauser effect (NOE) and amide exchange data, peptide 1 and its retro-inverso isomer 2 in the polar solvent environment of 40% d3-TFE/H2O at pH 2.3 show very similar topological features. However, in the relatively non-polar 300 mM SDS micellar environment, peptides 1 and 2 exhibit differences in their solution structures in terms of the amide backbone and side-chain orientations. In particular, under the SDS micellar condition, peptide 1 maintains much of the secondary structure observed for this 20-mer peptide in 40% d3-TFE/H2O, pH 2.3, whereas peptide 2 adopts a more extended structure. These NMR results provide the first confirmation that the secondary structure of the all L-a-peptide 1 is maintained in both polar and non-polar environments, whereas the secondary structure and topology of the notionally equivalent retro-inverso isomer depends more on the solvent conditions. These results with the all L-a-peptide 1 and its retro-inverso isomer 2 provide important insight into the conformational influences of the C- and N-end group with L-alpha- and retro-D-alpha-isomer pairs in non-polar environments, and thus have general relevance to the design of bioactive retro-inverso peptidomimetic analogues related to immunogenic or hormonal peptides.
...
PMID:Comparison of the solution conformations of a human immunodeficiency virus peptidomimetic and its retro-inverso isomer using 1H NMR spectroscopy. 944 43

The Rev protein of the human immunodeficiency virus type 1 (HIV-1) has been studied by time-resolved fluorescence spectroscopy. The single tryptophan residue of Rev, Trp45, located within the arginine-rich RNA-binding domain of the protein, was utilized as an intrinsic spectroscopic probe. In addition, five peptides spanning different lengths of the arginine-rich domain, each containing the tryptophan residue, and two C-terminal deletion mutants of Rev, Rev M9 delta 14 and Rev M11 delta 14, were examined. Rev M9 delta 14 lacks residues 68-112 whereas Rev M11 delta 14 is missing residues 92-112 of the C-terminus of Rev. The fluorescence decay of Trp45 in wild-type Rev was resolved into four discrete lifetime components, and decay-associated spectra (DAS) were obtained for each component. The fluorescence decays of all five peptides and Rev M9 delta 14 were resolved into three lifetime components. The fluorescence decay of Rev M11 delta 14 was resolved into four components similar to those found for wild-type Rev. These results indicate that the activation domain (residues 78-93), present in wild-type Rev and Rev M11 delta 14, induced a unique tryptophan environment, characterized by a short-lived, blue-shifted emission, attributed to higher order assembly of Rev. In addition, fluorescence anisotropy decay data obtained for wild-type Rev and the two C-terminal deletion mutants also indicate that the activation domain mediates self-association of Rev. Based on the anisotropy decay results for wild-type Rev, the distribution of oligomers is independent of salt concentration. The average fluorescence lifetime of Trp45 was reduced upon complexation of Rev with a 40-mer fragment of the Rev response element containing the minimal element for Rev binding (F8-RRE), and the emission was blue-shifted. In addition, the local rotation of the tryptophan side chain was blocked in the protein-RRE complex. These results indicate that Trp45 directly interacts with the RRE. Rev is also shown to bind to 5S RNA, resulting in very similar changes in the time-resolved tryptophan fluorescence to those observed upon complexation of Rev with F8-RRE.
...
PMID:Structural dynamics of HIV-1 Rev and its complexes with RRE and 5S RNA. 948 5

The high affinity and selectivity of nucleic acid ligands have clearly demonstrated that RNA can be targeted to a variety of molecules. In practice, however, the use of unmodified aptamers is impeded by the low stability of RNA in biological fluids. Here we describe the mirror-design of a stable 38-mer L-oligoribonucleotide ligand that binds to L-arginine. This L-RNA ligand was also able to bind to a short peptide containing the basic region of the human immunodeficiency virus type-1 Tat-protein. The L-RNA ligand displayed the expected stability in human serum. These findings may contribute to the identification of novel diagnostics and pharmaceuticals.
...
PMID:Mirror-design of L-oligonucleotide ligands binding to L-arginine. 963 Oct 62

A series of hexadeoxyribonucleotides (6-mers), d(TGGGAG), substituted with a variety of aromatic groups at the 5'-end were synthesized and tested for anti-human immunodeficiency virus type 1 (HIV-1) activity. While unmodified d(TGGGAG) (31) had no anti-HIV-1 activity, compound 23 with a 3,4-di(benzyloxy)benzyl (DBB) group at the 5'-end potently inhibited the HIV-1IIIB-induced cytopathicity of MT-4 cells in vitro (IC50 = 0.37 microM) without cytotoxicity up to 40 microM. A thermal denaturation study on the 5'-end-substituted 6-mers by means of the circular dichroism (CD) spectra demonstrated that the aromatic substituent attached at the 5'-end of the 6-mer strongly enhanced the formation of a parallel helical structure consisting of four strands (quadruplex). On the contrary, compound 36, in which one of the guanosines of 23 was replaced by a thymidine, did not form a quadruplex, thus exhibiting no anti-HIV-1 activity. Moreover, both compound 15, with a tert-butyldiphenylsilyl group solely at its 3'-end, and compound 21, with a relatively small substituent, a benzyl group, at the 5'-end, formed quadruplexes but had no anti-HIV-1 activity. These findings led us to the conclusion that both the quadruplex structure and the aromatic substituent with adequate size at the 5'-end are crucial for the interaction of the 5'-end-substituted 6-mers with the V3 loop as well as the CD4 binding site on viral gp120, resulting in anti-HIV-1 activity.
...
PMID:Biologically active oligodeoxyribonucleotides. 5. 5'-End-substituted d(TGGGAG) possesses anti-human immunodeficiency virus type 1 activity by forming a G-quadruplex structure. 973 90

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>