Modeling a Breast-Cancer Inhibiting Pharmacophore Based Upon the Activity of α -Fetoprotein Lower incidence of estrogen receptor positive (ER+) breast cancer in women has been attributed to the inhibitory activity of α -fetoprotein (AFP), a protein produced by the fetal yolk sac during pregnancy. 8-mer and cyclic 9-mer peptides derived from AFP have been shown to inhibit breast cancer in mouse and rat models. With the use of replica exchange molecular dynamics (REMD), we have worked to determine which behavior and structure aspects of these peptides result in the most effective breast-cancer inhibition. This has allowed us to narrow down the active region of AFP, and to establish methods that can be used as effective tools for predicting the biological activity of potential breast-cancer inhibiting pharmacophores. Proteasome Inhibitors Repurposed for the Study of Chlamydia Protease-like Activity Factor (CPAF): Efforts Towards the Development of an Anti-chlamydial Therapeutic Chlamydia trachomatis, an obligate intracellular bacterium, is the most common sexually transmitted pathogen in the developed world as well as the leading cause of infectious blindness worldwide. Recent studies strongly suggest that the survival of C. trachomatis is dependent upon the secretion of a number of effector molecules that interfere with host signaling. In particular, Chlamydia protease-like activity factor (CPAF) is a serine protease that has emerged as a potential virulence factor in chlamydial pathogenesis, however the exact role of CPAF remains unclear. Here we report efforts towards the synthesis of proteasome inhibitors and related derivatives that will be repurposed as CPAF inhibitors. We hypothesize that the utility of these inhibitors will be two-fold, in that they can be utilized as chemical biology tools for the study of CPAF, and further optimized as anti-chlamydial therapeutics.

Addressing problems at the interface of chemistry and medicine: Computational and chemical biology approaches

249th National Meeting (2015)

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