ADVERTISEMENT RETURN TO ISSUEPREVLab-ExptNEXTAssigning the NMR Spectrum of Glycidol: An Advanced Organic Chemistry ExerciseEric Helms , Nicholas Arpaia , and Melissa Widener View Author Information Department of Chemistry, State University of New York College at Geneseo, Geneseo, NY, 14454Cite this: J. Chem. Educ. 2007, 84, 8, 1328Publication Date (Web):August 1, 2007Publication History Received3 August 2009Published online1 August 2007Published inissue 1 August 2007https://pubs.acs.org/doi/10.1021/ed084p1328https://doi.org/10.1021/ed084p1328research-articleACS PublicationsRequest reuse permissionsArticle Views1418Altmetric-Citations8LEARN 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 SUBJECTS:Conformational analysis,Nuclear magnetic resonance spectroscopy,Organic chemistry,Students Get e-Alerts
Human Immunodeficiency Virus (HIV) type 1 uses a -1 programmed ribosomal frameshift (-1 PRF) event to translate its enzymes from the same transcript used to encode the virus' structural proteins. The frequency of this event is highly regulated, and significant deviation from the normal 5-10% frequency has been demonstrated to decrease viral infectivity. Frameshifting is primarily regulated by the Frameshift Stimulatory Signal RNA (FSS-RNA), a thermodynamically stable, highly conserved stem loop that has been proposed as a therapeutic target. We describe the design, synthesis, and testing of a series of N-methyl peptides able to bind the HIV-1 FSS RNA stem loop with low nanomolar affinity and high selectivity. Surface plasmon resonance (SPR) data indicates increased affinity is a reflection of a substantially enhanced on rate. Compounds readily penetrate cell membranes and inhibit HIV infectivity in a pseudotyped virus assay. Viral infectivity inhibition correlates with compound-dependent changes in the ratios of Gag and Gag-Pol in virus particles. As the first compounds with both single digit nanomolar affinities for the FSS RNA and an ability to inhibit HIV in cells, these studies support the use of N-methylation for enhancing the affinity, selectivity, and bioactivity of RNA-binding peptides.
The electrophilic addition of a hydrohalic acid (HX) to an alkene is often one of the first reactions learned in second-year undergraduate organic chemistry classes. During the ensuing discussion of the mechanism, it is shown that this reaction follows Markovnikov's rule, which states that the hydrogen atom will attach to the carbon with fewer substituents while the halogen atom will attach to the carbon with more substituents. However, in the preparation of tropic acid, the reaction of HCl with atropic acid (2-phenylpropenoic acid) does not follow this rule because it is a conjugated system. Molecular modeling of the possible carbocation intermediates suggests that the reaction follows a conjugate addition mechanism involving a 1,4-addition of HCl across the conjugated alkene and carboxyl group rather than addition across the alkene as students often first propose. PM3 semiempirical calculations are used to determine the energies of three possible carbocation intermediates. The energies obtained from the modeling suggest that the carbocation intermediate produced by the 1,4-addition is the most stable.
The HIV-1 frameshift-stimulating (FSS) RNA, a regulatory RNA of critical importance in the virus' life cycle, has been posited as a novel target for anti-HIV drug development. We report the synthesis and evaluation of triazole-containing compounds able to bind the FSS with high affinity and selectivity. Readily accessible synthetically, these compounds are less toxic than previously reported olefin congeners. We show for the first time that FSS-targeting compounds have antiviral activity against replication-competent HIV in human cells, including a highly cytopathic, multidrug-resistant strain. These results support the viability of the HIV-1 FSS RNA as a therapeutic target and more generally highlight opportunities for synthetic molecule-mediated interference with protein recoding in a wide range of organisms.
Working collaboratively, chemistry faculty members and librarians developed an exercise to introduce students in a large organic chemistry course to SciFinder and the chemical literature. Students learn fundamental concepts about the nature of the scientific literature through preclass readings, a preclass assignment, and an in-class discussion. Once students are familiar with several types of scientific literature (research articles, review articles, news articles) and peer review, they can more effectively search SciFinder to find scientific information. During class, students explore chemical data (including spectra) and learn to use SciFinder's natural language interface for searching the chemical literature. Assessment results demonstrated that students were learning about SciFinder for the first time and were impressed with the information available. Students were also successful at distinguishing between article types and recalling several methods of searching SciFinder.
We have carried out a comprehensive study that analyzes the evolution of catalytic activity in the polyclonal antibodies elicited by a phosphate hapten over the course of an immunization regimen. We have found that catalytic activity elicited by the phosphate hapten 1, measured as apparent kcat for the hapten-specific fraction of polyclonal antibodies, increased through the first four or five immunizations, then decreased to differing extents in both of the rabbits studied. The initial increase in catalytic activity was correlated with increasing hapten affinity, but then hapten affinity remained high while catalytic activity decreased later in the response. These results indicate that consideration must be given to the temporal aspects of the catalytic immune response before any global conclusions are reached, e.g., a simple correlation of catalytic activity with hapten affinity. In addition, it is clear that the number of immunizations is an important parameter that must be considered when attempting to optimize antibody catalytic activity, and that more immunizations are not necessarily better.
Stercobilin is an end‐stage metabolite of hemoglobin, a component of red blood cells. It has been found that there is a significantly lower concentration of stercobilin in the urine of people diagnosed with autism spectrum disorders, suggesting potential use as a biomarker. In vitro, we have synthesized stercobilin from its precursor bilirubin through a reduction reaction proceeded by an oxidation reaction. In addition, we have isotopically labeled the stercobilin product with deuterium using this protocol. Nuclear magnetic resonance investigations show the products of the unlabeled stercobilin (Rxn 1) and the deuterated stercobilin (Rxn 2) both had a loss of signals in the 5.0‐ to 7.0‐ppm range indicating proper conversion to stercobilin. Changes in the multiplicity of the sp3 region of the proton nuclear magnetic resonance suggest proper deuterium incorporation. Mass spectrometry studies of Rxn 1 show a difference in fragmentation patterns than that of Rxn 2 proposing potential locations for deuterium incorporation. This isotopologue of stercobilin is stable (>6 mo), and further analysis permits investigation for its use as a biomarker and potential quantitative diagnostic probe for autism spectrum disorders.
