ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPurification, characterization, and amino acid sequence of rat anaphylatoxin (C3a)John W. Jacobs, Jeffrey S. Rubin, Tony E. Hugli, Richard A. Bogardt, Ida K. Mariz, John S. Daniels, William H. Daughaday, and Ralph A. BradshawCite this: Biochemistry 1978, 17, 23, 5031–5038Publication Date (Print):November 14, 1978Publication History Published online1 May 2002Published inissue 14 November 1978https://pubs.acs.org/doi/10.1021/bi00616a027https://doi.org/10.1021/bi00616a027research-articleACS PublicationsRequest reuse permissionsArticle Views72Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

Anaphylatoxin

Sequence (biology)

Characterization

10.1021/bi00616a027

Cite

Citations (37)

Kinetics and Mechanism of the General-Acid-Catalyzed Ring-Closure of the Malondialdehyde−DNA Adduct, N²-(3-Oxo-1-propenyl)deoxyguanosine (N²OPdG^-), to 3-(2‘-Deoxy-β-d-erythro-pentofuranosyl)pyrimido[1,2-α]purin- 10(3H)-one (M₁dG)

Journal of the American Chemical Society (2004)

James N. Riggins Derek A. Pratt Markus Voehler J. Scott Daniels Lawrence J. Marnett

3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M1dG) is the major product of the reaction of deoxyguanosine with malondialdehyde (MDA). M1dG blocks replication by DNA polymerases in vitro and is mutagenic in vivo. M1dG reacts with hydroxide to form the N2-(3-oxo-1-propenyl)deoxyguanosine anion (N2OPdG-). This reaction is pH-dependent and reverses under neutral and acidic conditions to form M1dG. Here we describe the kinetics and mechanism of the ring-closure reaction in both the nucleoside and oligonucleotides. Kinetic analysis of absorbance and fluorescence changes demonstrates that ring-closure is biphasic, leading to the rapid formation of an intermediate that slowly converts to M1dG in a general-acid-catalyzed reaction. The dependence of the rate of the rapid phase on pH reveals the pKa for protonated N2OPdG is 6.9. One-dimensional 1H NMR and DQF-COSY experiments identified two distinct intermediates, N2OPdG-H and 8-hydroxy-6,7-propenodeoxyguanosine (HO-Prene-dG), that are formed upon acidification of N2OPdG-. Characterization of ring-closure in single-stranded and in melted duplex oligonucleotides shows M1dG formation is also acid-catalyzed in single-stranded oligonucleotides and that the denaturation of an oligonucleotide duplex enhances ring-closure. This work details the complexity of ring-closure in the nucleoside and oligonucleotides and provides new insight into the role of duplex DNA in catalyzing ring-opening and ring-closing of M1dG and N2OPdG.

Deoxyguanosine

10.1021/ja040010q

Cite

Citations (40)

Table 4, SAR Analysis for rat M4 Positive Allosteric Modulators

Thomas M. Bridges Colleen M. Niswender Carrie K. Jones L. Michelle Lewis C. David Weaver

Table (database)

Source

Cite

Citations (0)

Neurovascular unit on a chip: implications for translational applications

Stem Cell Research & Therapy (2013)

Donald J. Alcendor Frank E. Block David E. Cliffel J. Scott Daniels Kate L. J. Ellacott

The blood-brain barrier (BBB) dynamically controls exchange between the brain and the body, but this interaction cannot be studied directly in the intact human brain or sufficiently represented by animal models. Most existing in vitro BBB models do not include neurons and glia with other BBB elements and do not adequately predict drug efficacy and toxicity. Under the National Institutes of Health Microtissue Initiative, we are developing a three-dimensional, multicompartment, organotypic microphysiological system representative of a neurovascular unit of the brain. The neurovascular unit system will serve as a model to study interactions between the central nervous system neurons and the cerebral spinal fluid (CSF) compartment, all coupled to a realistic blood-surrogate supply and venous return system that also incorporates circulating immune cells and the choroid plexus. Hence all three critical brain barriers will be recapitulated: blood-brain, brain-CSF, and blood-CSF. Primary and stem cell-derived human cells will interact with a variety of agents to produce critical chemical communications across the BBB and between brain regions. Cytomegalovirus, a common herpesvirus, will be used as an initial model of infections regulated by the BBB. This novel technological platform, which combines innovative microfluidics, cell culture, analytical instruments, bioinformatics, control theory, neuroscience, and drug discovery, will replicate chemical communication, molecular trafficking, and inflammation in the brain. The platform will enable targeted and clinically relevant nutritional and pharmacologic interventions for or prevention of such chronic diseases as obesity and acute injury such as stroke, and will uncover potential adverse effects of drugs. If successful, this project will produce clinically useful technologies and reveal new insights into how the brain receives, modifies, and is affected by drugs, other neurotropic agents, and diseases.

Organ-on-a-Chip

Neurovascular bundle

10.1186/scrt379

Cite

Citations (84)

Relationship between In Vivo Receptor Occupancy and Efficacy of Metabotropic Glutamate Receptor Subtype 5 Allosteric Modulators with Different In Vitro Binding Profiles

Neuropsychopharmacology (2014)

Jerri M. Rook Mohammed Noor Tantawy M. Sib Ansari Andrew S. Felts Shaun R. Stauffer

Radioligand

Allosteric modulator

10.1038/npp.2014.245

Cite