A5037802350- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Bacteriophages and microbial interactions
- Click Chemistry and Applications
- Plant Virus Research Studies
- HIV/AIDS Research and Interventions
- Chemical Synthesis and Analysis
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- DNA and Nucleic Acid Chemistry
- Pneumocystis jirovecii pneumonia detection and treatment
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Malaria Research and Control
- Protease and Inhibitor Mechanisms
- Enzyme Production and Characterization
- Viral gastroenteritis research and epidemiology
- Carbohydrate Chemistry and Synthesis
- Plant and Fungal Interactions Research
- Biochemical and Structural Characterization
- Metal complexes synthesis and properties
- HIV-related health complications and treatments
- Transgenic Plants and Applications
Nemours Children's Clinic
2021-2024
Nova Southeastern University
2016-2017
Sequoia (United States)
2006-2012
Frederick National Laboratory for Cancer Research
1993-2006
Science Applications International Corporation (United States)
1995-2005
National Cancer Institute
1993-2005
National Institutes of Health
1994-2000
LabCorp (United States)
1992-2000
New Frontier
1998
Cornell University
1998
An improved protocol for crystallographic refinement by simulated annealing is presented. It consists of slow cooling starting at high temperatures. Tests refinements aspartate aminotransferase and procin pepsin show that the slow-cooling produces lower R factors better geometry than other protocols previously published. The influence temperature-control method, weighting, rate duration heating stage on success studied. Analysis time course potential-energy fluctuations indicates no global...
A two-fold ( C 2 ) symmetric inhibitor of the protease human immunodeficiency virus type-1 (HIV-1) has been designed on basis three-dimensional symmetry enzyme active site. The molecule inhibited both activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against than related enzymes, appeared to be stable degradative enzymes. 2.8 angstrom crystal structure inhibitor-enzyme complex demonstrated that binds a highly fashion.
Objective: It is thought as a consequence of continuous replication, HIV-1 has acquired an optimal fitness state and that suboptimal antiretroviral therapy selects for drug resistant variants which show impaired in the absence drug. In this paper we studied evolution viral populations appearing patient who received protease monotherapy. Methods: Two factors contributing to fitness, resistance catalytic activity, were at enzymatic virological level. Results: The first selected vivo harboured...
Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures cathepsin complex with pepstatin at 2.5 A resolution provides insights into inhibitor binding targeting for this two-chain, N-glycosylated aspartic protease. Comparison bound rhizopuspepsin human renin-inhibitor revealed differences subsite inhibitor-enzyme interactions that...
Plasmodium falciparum is the major causative agent of malaria, a disease worldwide importance. Resistance to current drugs such as chloroquine and mefloquine spreading at an alarming rate, our antimalarial armamentarium almost depleted. The malarial parasite encodes two homologous aspartic proteases, plasmepsins I II, which are essential components its hemoglobin-degradation pathway novel targets for drug development. We have determined crystal structure recombinant plasmepsin II complexed...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic Characterization and Cross-Resistance Patterns Of HIV-1 Protease Mutants Selected under Drug PressureSergei V. Gulnik, Leonid I. Suvorov, Beishan Liu, Betty Yu, Barry Anderson, Hiroaki Mitsuya, John W. EricksonCite this: Biochemistry 1995, 34, 29, 9282–9287Publication Date (Print):July 25, 1995Publication History Published online1 May 2002Published inissue 25 July...
Tumor suppressor protein p53 is a tetrameric phosphoprotein that activates transcription from several cell cycle regulating genes in response to DNA damage. Tetramer formation critical p53's ability activate transcription; however, posttranslational modifications and stabilization also contribute transcription. To determine if phosphorylation affects tetramer formation, we synthesized phosphopeptides corresponding residues 303-393 of human p53, which includes the domain responsible for...
Inhibitors of the human immunodeficiency virus protease represent a promising new class antiretroviral drugs for treatment AIDS. We now report in vitro selection viral variants with decreased sensitivity to symmetry-based inhibitor, ABT-538, currently being tested clinical trials. Molecular characterization shows that an isoleucine-to-valine substitution at position 84 results substantial decrease drug. Moreover, additional mutation 82, valine phenylalanine, further decreases susceptibility...
Inhibitors of the human immunodeficiency virus type 1 protease represent a promising class antiviral drugs for treatment AIDS, and several are now in clinical trials. Here, we report vitro selection viral variants with decreased sensitivity to C2-symmetric inhibitor (A-77003). We show that single amino acid substitution (Arg Gln or Lys) at position 8 results substantial decrease inhibitory activity drug on enzyme comparable increase resistance. These findings, when analyzed by using...
Inhibitors of the human immunodeficiency virus type 1 (HIV-1) protease represent a promising addition to available agents used inhibit replication in therapeutic setting. HIV-1 is capable generating phenotypic variants face variety selective pressures. The potential generate with reduced sensitivity inhibitor was examined by selecting for growth cell culture presence A-77003. Virus grew out inhibitor, and these encoded proteases inhibitor. Variants were identified that changes each three...
We have evaluated the sequence diversity of protease human immunodeficiency virus type 1 in vivo. Our analysis 246 coding domain sequences obtained from 12 subjects indicates that amino acid substitutions predicted to give rise inhibitor resistance may be present patients who not received inhibitors. In addition, we demonstrated residues directly involved enzyme-substrate interactions varied infected individuals. Several these occurred combination either more or less frequently than would...
ABSTRACT We identified UIC-94003, a nonpeptidic human immunodeficiency virus (HIV) protease inhibitor (PI), containing 3( R ),3a( S ),6a( )- bis -tetrahydrofuranyl urethane ( -THF) and sulfonamide isostere, which is extremely potent against wide spectrum of HIV (50% inhibitory concentration, 0.0003 to 0.0005 μM). UIC-94003 was also multi-PI-resistant HIV-1 strains isolated from patients who had no response any existing antiviral regimens after having received variety agents 0.0055 Upon...
The nucleocapsid (NC) protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is important for encapsidation the genome, RNA dimerization, and primer tRNA annealing in vitro. Here we present evidence from gel mobility-shift experiments indicating that binds specifically to an sequence. Two complexes were identified native gels. more slowly migrating complex contained two molecules one peptide, while rapidly composed peptide. Further, mutational analysis shows predicted stem loop...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfluence of stereochemistry on activity and binding modes for C2 symmetry-based diol inhibitors HIV-1 proteaseMadhusoodan V. Hosur, T. Narayana Bhat, Dale J. Kempf, Eric Baldwin, Beishan Liu, Sergei Gulnik, Norman E. Wideburg, Daniel W. Norbeck, Krzysztof Appelt, John EricksonCite this: Am. Chem. Soc. 1994, 116, 3, 847–855Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February...
Abstract The sequence‐specific DNA binding of recombinant p42 and p51 ETSl oncoprotein was examined quantitatively to determine whether the loss Exon VII phosphorylation domain in or expressed had an effect on activity. kinetics measured using real‐time changes surface plasmon resonance with BIAcore (registered trademark, Pharmacia Biosensor) technology. displayed significant differences kinetic behavior. is characterized by a fast initial conversion stable complex, whereas exhibits slow...
Abstract A revised three‐dimensional crystal structure of ethanol‐inhibited porcine pepsin refined to an R ‐factor 0.171 at 2.3 Å resolution is presented and compared the structures fungal aspartic proteinases: penicillopepsin, rhizopuspepsin, endothiapepsin. Pepsin composed two nearly equal N C domains related by intra dyad. The overall polypeptide fold active site are homologous for enzymes. weak inhibition ethanol can be explained presence one or more molecules, in vicinity carboxylates,...
<h3>Importance</h3> This is the first large-scale randomized clinical trial evaluating effectiveness and safety of overminus spectacle therapy for treatment intermittent exotropia (IXT). <h3>Objective</h3> To evaluate spectacles to improve distance IXT control. <h3>Design, Setting, Participants</h3> conducted at 56 sites between January 2017 2019 associated with Pediatric Eye Disease Investigator Group enrolled 386 children aged 3 10 years IXT, a mean control score 2 or worse, refractive...
Transition state mimetic tripeptide human immunodeficiency virus (HIV) protease inhibitors containing allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid] were synthesized and tested for activity against HIV in vitro. Two compounds, KNI-227 KNI-272, which highly potent with little inhibition of other aspartic proteases, showed the most infectivity cytopathic effect a wide spectrum strains. As target CD4+ ATH8 cells, 50% inhibitory concentrations type 1 LAI (HIV-1LAI),...
We designed, synthesized, and identified JE-2147, an allophenylnorstatine-containing dipeptide HIV protease inhibitor (PI), which is potent against a wide spectrum of HIV-1, HIV-2, simian immunodeficiency virus, various clinical HIV-1 strains in vitro . Drug-resistant strains, isolated from seven patients who had failed 9–11 different anti-HIV therapeutics after 32–83 months, variety drug-resistance-related amino acid substitutions were highly invariably resistant to all the currently...