A5039449131- Monoclonal and Polyclonal Antibodies Research
- Hemoglobin structure and function
- thermodynamics and calorimetric analyses
- Protein purification and stability
- Heme Oxygenase-1 and Carbon Monoxide
- Protein Structure and Dynamics
- Neonatal Health and Biochemistry
- Viral Infectious Diseases and Gene Expression in Insects
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Advanced Biosensing Techniques and Applications
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Mass Spectrometry Techniques and Applications
- Wastewater Treatment and Nitrogen Removal
- Computational Drug Discovery Methods
- HIV Research and Treatment
- Erythrocyte Function and Pathophysiology
- HIV/AIDS drug development and treatment
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Thermodynamic and Structural Properties of Metals and Alloys
- Biochemical and Structural Characterization
Assumption College
2023
Bristol-Myers Squibb (United States)
2010-2021
Evoqua Water Technologies (United States)
2015-2018
Bristol-Myers Squibb (Germany)
2002-2015
Protein Express (United States)
2015
Google (United States)
2015
Minnesota State University, Mankato
2015
Novartis Institutes for BioMedical Research
2014
Pathways Behavioral Services
2014
Novartis (Switzerland)
2014
The site of action a series pyridinyl imidazole compounds that are selective inhibitors p38 mitogen-activated protein kinase in vitro and block proinflammatory cytokine production vivo has been determined. Using Edman sequencing, 125I-SB206718 was shown to cross-link the nonphosphorylated Escherichia coli-expressed at Thr175, which is proximal ATP binding site. Titration calorimetric studies withE. showed SB203580 bound with stoichiometry 1:1 blocked by preincubation analogue, FSBA...
HIV infection is initiated by the selective interaction between cellular receptor CD4 and gp120, external envelope glycoprotein of virus. We used analytical ultracentrifugation, titration calorimetry, surface plasmon resonance biosensor analysis to characterize assembly state, thermodynamics, kinetics CD4-gp120 interaction. The binding thermodynamics were unexpected magnitude; changes in enthalpy, entropy, heat capacity greatly exceeded those described for typical protein-protein...
Interleukin-1 (IL-1), fibroblast growth factors (FGFs), and their homologues are secreted that share a common β-barrel structure act on target cells by binding to cell surface receptors with immunoglobulin-like folds in extracellular domain. While numerous members of the FGF family have been discovered, IL-1 has remained small outnumbered receptor homologues. From expressed sequence tag data base searches, we now identified four additional homologues, IL-1H1, IL-1H2, IL-1H3, IL-1H4. Like...
Although tetrameric hemoglobin has been studied extensively as a prototype for understanding mechanisms of allosteric regulation, the functional and structural properties its eight intermediate ligation forms have remained elusive. Recent experiments on energetics cooperativity these intermediates, along with assignments their quaternary structures, revealed that mechanism is controlled by previously unrecognized symmetry feature: switching from form T to R occurs whenever heme-site binding...
TRAIL is a member of the tumor necrosis factor (TNF) family cytokines which induces apoptotic cell death in variety lines. It mediates its effects through one two receptors, DR4 and DR5, are members TNF receptor family, whose cytoplasmic regions contain domains. In addition, also binds to 3 "decoy" DcR2, with truncated domain, DcR1, glycosylphosphatidylinositol-anchored receptor, OPG secreted protein known bind another RANKL. However, although apoptosis depends on expression or both domain...
Using BIAcore technology, we determined the rate constants for a protein antigen-antibody interaction that was mass transport limited on optical biosensor. The antigen consisted of soluble form human T-cell receptor CD4 (two amino terminal domains, D1D2) and antibody an anti-CD4 monoclonal from monkey engineered with constant domains IgG1. High quality response data were obtained this by orienting attachment sensor surface correcting instrument artifacts control experiments. numerical...
ABSTRACT The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein is conformationally flexible. Upon binding to the host cell receptor CD4, assumes a conformation that recognized by second receptor, CCR5 and/or CXCR4, and CD4-induced (CD4i) antibodies. Guided X-ray crystal structure of gp120-CD4-CD4i antibody complex, we introduced changes into were designed stabilize or disrupt this conformation. One mutant, 375 S/W, in which tryptophan indole group predicted...
Abstract Purpose: PIM kinases have been shown to act as oncogenes in mice, with each family member being able drive progression of hematologic cancers. Consistent this, we found that PIMs are highly expressed human cancers and show isoform has a distinct expression pattern among disease subtypes. This suggests inhibitors all three would be effective treating multiple malignancies. Experimental Design: Pan-PIM proven difficult develop because PIM2 low Km for ATP and, thus, requires very...
ADVERTISEMENT RETURN TO ISSUEPREVarticleNEXTDetermination of the monomer-dimer equilibrium interleukin-8 reveals it is a monomer at physiological concentrationsStephen D. Burrows, Michael L. Doyle, Kenneth P. Murphy, Samuel G. Franklin, John R. White, Ian Brooks, Dean E. McNulty, Miller O. Scott, Jay Knutson, Denise Porter, Peter Young, and Preston HensleyCite this: Biochemistry 1994, 33, 43, 12741–12745Publication Date (Print):January 1, 1994Publication History Published online1 November...
Abstract Several CD4 mAbs have entered the clinic for treatment of autoimmune diseases or transplant rejection. Most these caused cell depletion, and some were murine which further hampered by human anti-mouse Ab responses. To obviate concerns, a primatized mAb, clenoliximab, was generated fusing V domains cynomolgus macaque mAb to constant regions. The heavy chain region is modified IgG4 containing two single residue substitutions designed ablate residual Fc receptor binding activity...
Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, P. represents a highly attractive target novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed variable aromatic ring, one four...
Engineered domains of human fibronectin (Adnectins™) were used to generate a bispecific Adnectin targeting epidermal growth factor receptor (EGFR) and insulin-like factor-I (IGF-IR), two transmembrane receptors that mediate proliferative survival cell signaling in cancer. Single-domain Adnectins specifically bind EGFR or IGF-IR generated using mRNA display with library containing as many 1013 variants. was also optimize lead affinities, resulting clones inhibited phosphorylation at 7 38 nM...
The aim of this research is to determine the effect process parameters Binder Jet manufactured Stainless Steel 420 + Bronze parts on mechanical properties such as tensile strength, yield strength and elastic modulus. Different layer thickness part orientation during printing were varied. A full factorial design experiments matrix was made by varying 3 different thicknesses (50 μm, 100 μm 200 μm) 5 angles in planes. ASTM E8 standard used for testing specimen results compared. showed that...
The catalytic (C) subunit of cAMP-dependent protein kinase (cAPK) is more stable by several criteria when it part a holoenzyme complex. By measuring the thermal stability free C in presence and absence nucleotides and/or divalent metal ions, was found that most stabilizing effects associated with type I could be attributed to nucleotide. specific requirements for this enhanced were further dissected: Adenosine stabilized up 5 °C; however, cations (i.e., Mg2+, Ca2+, Mn2+) do not increase heat...
In the bacterial type II fatty acid synthase system, β-ketoacyl-acyl carrier protein (ACP) III (FabH) catalyzes condensation of acetyl-CoA with malonyl-ACP. We have identified, expressed, and characterized the<i>Streptococcus pneumoniae</i> homologue <i>Escherichia coli</i> FabH. <i>S. FabH is ∼41, 39, 38% identical in amino sequence to <i>Bacillus subtilis</i>,<i>E. coli,</i> <i>Hemophilus influenzae</i> FabH, respectively. The His-Asn-Cys catalytic triad present other molecules conserved...
Two humanized monoclonal antibodies, MEDI-493 and RSHZl9, were developed independently as potential improvements over RSV-IGIV for prevention of respiratory syncytial virus (RSV) infection. is a polyclonal human antibody preparation intravenous infusion enriched RSV neutralizing activity. A phase III clinical trial showed that significantly reduced hospitalizations due to In separate trial, RSHZl9 failed show significant efficacy. new studies, the in vitro vivo activities compared determine...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxygen binding constants for human hemoglobin tetramersStanley J. Gill, Enrico Di Cera, Michael L. Doyle, Gary A. Bishop, and Charles H. RobertCite this: Biochemistry 1987, 26, 13, 3995–4002Publication Date (Print):June 30, 1987Publication History Published online1 May 2002Published inissue 30 June 1987https://pubs.acs.org/doi/10.1021/bi00387a038https://doi.org/10.1021/bi00387a038research-articleACS PublicationsRequest reuse permissionsArticle...
This paper describes the design and characterization of novel inhibitors IleRS, whose binding affinity approaches tightest reported for noncovalent inhibition. Compounds were designed from a model natural product pseudomonic acid-A (PS-A) together with detailed understanding reaction cycle IleRS mode intermediate IleAMP. The interactions compounds characterized by inhibition aminoacylation tRNA or PP(i)/ATP exchange at supersaturating substrate concentration transient kinetics calorimetry...
The steady-state kinetics of a full-length and truncated form the type 2 human methionine aminopeptidase (hMetAP2) were analyzed by continuous monitoring amide bond cleavage various peptide substrates methionyl analogues 7-amido-4-methylcoumarin (AMC) p-nitroaniline (pNA), utilizing new fluorescence-based absorbance-based assay novel coupled-enzyme method. most efficient for hMetAP2 appeared to be peptides three or more amino acids which values k(cat)/K(m) approximately 5 x 10(5) M(-1)...