A5032012119- DNA and Nucleic Acid Chemistry
- Metal complexes synthesis and properties
- Scientific Computing and Data Management
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Biomedical Text Mining and Ontologies
- HER2/EGFR in Cancer Research
- Advanced biosensing and bioanalysis techniques
- Research Data Management Practices
- Lung Cancer Treatments and Mutations
- Phosphodiesterase function and regulation
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Genetics, Bioinformatics, and Biomedical Research
- Chemical Synthesis and Analysis
- Metal-Catalyzed Oxygenation Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Semantic Web and Ontologies
- Antibiotic Resistance in Bacteria
- Tuberculosis Research and Epidemiology
- Cell Image Analysis Techniques
- Cytokine Signaling Pathways and Interactions
- Data Quality and Management
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
Digital Catapult (United Kingdom)
2024
Bristol-Myers Squibb (United States)
2020-2021
GlaxoSmithKline (United States)
2004-2011
Research Triangle Park Foundation
2004-2011
GlaxoSmithKline (Netherlands)
2008
Chemo (France)
2006
Merck & Co., Inc., Rahway, NJ, USA (United States)
1996-2001
Infectious Diseases and the Research Institute
1999
Scripps Research Institute
1998
Albert Einstein College of Medicine
1996-1998
Cyclic nucleotides are second messengers that essential in vision, muscle contraction, neurotransmission, exocytosis, cell growth, and differentiation. These molecules degraded by a family of enzymes known as phosphodiesterases, which serve critical function regulating the intracellular concentration cyclic nucleotides. We have determined three-dimensional structure catalytic domain phosphodiesterase 4B2B to 1.77 angstrom resolution. The active site has been identified contains cluster two...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBleomycins: A Structural Model for Specificity, Binding, and Double Strand CleavageJoAnne Stubbe, John W. Kozarich, Wei Wu, Dana E. VanderwallView Author Information Departments of Chemistry Biology, Massachusetts Institute Technology, Cambridge, 02139, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900Cite this: Acc. Chem. Res. 1996, 29, 7, 322–330Publication Date (Web):July 11, 1996Publication History Received1 January...
Analysis of the x-ray crystal structure mono-substituted acetylenic thienopyrimidine 6 complexed with ErbB family enzyme ErbB-4 revealed a covalent bond between terminal carbon acetylene moiety and sulfhydryl group Cys-803 at solvent interface. The identification this adduct suggested that related analogs might also be capable forming an analogous EGFR, which has conserved cysteine (797) near ATP binding pocket. To test hypothesis, we treated truncated, catalytically competent form EGFR...
Bleomycin is a metal- and oxygen-dependent DNA cleaver. The chemistry of damage has been proposed to involve rate-limiting abstraction the 4′-hydrogen. A fragment prepared that contains [4′- 2 H]thymidine residues high isotopic content. Primary kinetic isotope effects have directly observed at individual thymidine with sequencing technology.
The solution structure of Co·Bleomycin (CoBLM) A2 green (the hydroperoxide form CoBLM) complexed with the self-complementary oligonucleotide d(CCAGGCCTGG) a cleavage site at C6 has been determined by 2D NMR spectroscopic methods and molecular dynamics calculations. Intermolecular NOEs (60 between CoBLM DNA) intramolecular (61 within green) have defined position orientation respect to its single binding in duplex. is stable analog activated BLM, Fe3+ (Sam, J. W.; Tang, X.-J.; Peisach, Am....
The structure of homogeneous Co·Bleomycin (CoBLM) A2 green (the hydroperoxide form CoBLM) has been determined using 2D NMR methods and molecular dynamics calculations. Previous studies Xu et al. (Xu, R. X.; Nettesheim, D.; Otvos, J. Petering, D. H. Biochemistry 1994, 33, 907−916) reported several possible structures for CoBLM compatible with their data acquired on a mixture brown forms. availability the pure green, which is stable months at neutral pH, allowed complete assignments 1H 13C...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInteraction of Co.cntdot.Bleomycin A2 (Green) with d(CCAGGCCTGG)2: Evidence for Intercalation Using 2D NMRWei Wu, Dana E. Vanderwall, JoAnne Stubbe, John W. Kozarich, and Chris J. TurnerCite this: Am. Chem. Soc. 1994, 116, 23, 10843–10844Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November...
Numerous biochemical and structural studies have shown that the conformation of estrogen receptor alpha (ERalpha) can be influenced by ligand binding. In turn, conformational state ERalpha affects ability to interact with a wide variety protein accessory factors. To globally investigate ligand-based cofactor recruitment activities ERalpha, we applied flow cytometric multiplexed binding assay determine simultaneous over 50 different peptides derived from both known proteins random peptide...
A model for the structure of aquated form cobalt bleomycin (H2O-CoBLM or CoBLM A2 brown), free and bound to d(CCAGGCCTGG)2 (1) is reported based on molecular modeling using constraints obtained from 2D NMR studies. brown has a chiral organization its ligands, including axial primary amine β-aminoalanine, identical hydroperoxide BLM (HOO-CoBLM green). H2O-CoBLM forms 1:1 complex with 1 Kd 2 × 10-6 M which in slow exchange time scale. The exhibits 44 intermolecular NOEs 56 intramolecular...
NMR studies of the hydroperoxide form cobalt deglycoBleomycin A2 (HOO−CodGBLM) and its complex with oligonucleotide d(CCAGGCCTGG) (1, C is site cleavage) are presented in an effort to establish deglycoBLM as a prototype for BLM analogues, synthesized without sugar moieties (Boger et al. Bioorg. Med. Chem. 1995, 3, 1281−1295). The structure determination free HOO−CodGBLM has been hampered by lack NOE or ROE information. By direct comparison chemical shifts coupling constants glycosylated...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDegradation of DNA-RNA hybrids by bleomycin: evidence for DNA strand specificity and possible structural modulation chemical mechanismC. R. Krishnamoorthy, Dana E. Vanderwall, John W. Kozarich, JoAnne. StubbeCite this: J. Am. Chem. Soc. 1988, 110, 6, 2008–2009Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March...
Abstract The mode of inactivation glutathione S-transferase isoenzyme 3-3 from rat by the active site-directed inhibitor 2-(S-glutathionyl)-3,5,6-trichloro-1,4-benzoquinone (GSTCBQ) has been investigated a combination site-specific mutagenesis and mass spectrometric analysis sites reaction reagent with enzyme. This very reactive is shown to target 3 residues in or near site, including hydroxyl groups Tyr-6 Tyr-115 sulfhydryl group Cys-114. Although covalent attachment one...
Retrieving pertinent information from biological scientific literature requires cutting-edge text mining methods which may be able to recognize the meaning of very ambiguous names entities. Aliases a gene share common vocabulary in their respective collections PubMed abstracts. This true even when these aliases are not associated with same subset documents. gene-specific defines unique fingerprint that can used disclose aliases. The present work describes an original method for automatically...
Abstract Quantitatively determining in vivo achievable drug concentrations targeted organs of animal models and subsequent target engagement confirmation is a challenge to discovery translation due lack bioassay technologies that can discriminate binding with different mechanisms. We have developed multiplexed high-throughput method quantify distribution tissues by integrating high content screening (HCS) U-Net based deep learning (DL) image analysis models. This technology combination...