Comparison of Experimental and Theoretical Structures of a Transition State Analogue Used for the Induction of Anti-Cocaine Catalytic Antibodies

Comparison of the crystal structure of a transition state analogue that was used to raise catalytic antibodies for the benzoyl ester hydrolysis of cocaine with structures calculated by ab initio, semiempirical, and solvation semiempirical methods reveals that modeling of solvation is crucial for replicating the crystal structure geometry. Both SM3 and SM2 calculations, starting from the crystal structure TSA I, converged on structures similar to the crystal structure. The 3-21G(*)/HF, 6-31G*/HF, PM3, and AM1 calculations converged on structures similar to each other, but these gas-phase structures were significantly extended relative to the condensed phase structures. Two transition states for the hydrolysis of the benzoyl ester of cocaine were located with the SM3 method. The gas phase calculations failed to locate reasonable transition state structures for this reaction. These results imply that accurate modeling of the potential energy surfaces for the hydrolysis of cocaine requires solvation methods.

Computational Design and Experimental Discovery of an Anti-estrogenic Peptide Derived from Alpha-Fetoprotein

Breast cancer is the most common cancer among women, and tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment. Many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Consequently, there is an ongoing need for breast cancer drugs that have different molecular targets. Previous work has shown that 8-mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat models, interacting with an unsolved receptor, while peptides smaller than eight amino acids did not. We show that the use of replica exchange molecular dynamics predicts the structure and dynamics of active peptides, leading to the discovery of smaller peptides with full biological activity. Simulations identified smaller peptide analogues with the same conserved reverse turn demonstrated in the larger peptides. These analogues were synthesized and shown to inhibit estrogen-dependent cell growth in a mouse uterine growth assay, a test showing reliable correlation with human breast cancer inhibition.

'Initiators of Discursive Practices': Authorship, attribution, and intent in the debates between philosophes and anti-philosophes

This article focuses on the “social side” of pseudonymity—on how writers and readers compete to influence the critical destiny of a pseudonymous work. By analyzing pseudonymity and attribution in both the specific context of Voltaire’s 1760 staging of the play, Le café ou l’écossaise, and in larger debates in the emerging fields of anonymity, pseudonymity, and attribution studies, I hope to show how literary scholars at present can address the individuality of each pseudonymous case while not letting go of trans-historical, general problems of anonymous strategies. Voltaire’s use of multiple pseudonyms before and after releasing L’Ecossaise, a comédie sérieuse in which Voltaire attacks his enemy Elie-Cathérine Fréron, supports his philosophe friends at a crucial moment in history, and exemplifies his emerging taste for serious comedy and British drama calls into question traditional takes on pseudonymity, anonymity, and attribution by refusing to fit into the binary arguments of anonymous vs. attributed and authorial intent vs. the reader’s control.