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 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.

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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.