Abstract. Background The management of prostate cancer is a significant healthcare challenge. Many treatment options exist (1-3), with radiation therapy playing a prominent role. However, the morbidity and cost of treatment are not trivial (4, 5). Although risk classification schemes (6) and nomograms (7) attempt to identify men most likely to benefit from treatment, it remains difficult to balance the risks of disease progression against competing risks of mortality (8). This has resulted in controversy over prostate-specific antigen (PSA) screening (9, 10) and possible overtreatment leading to a decreased quality of life (5, 11). Therefore, it is of great interest to conduct research into cancer prevention strategies (12), identification of men who will benefit most from treatment, and effective therapies that limit treatment-related morbidity of prostate cancer.Statins or 3-hydroxyl-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors are widely used medications for hypercholesterolaemia. The demographics of prostate cancer and hypercholesterolaemia overlap. The prevalence of statin use in this older men population is high-approximately 24 million Americans in 2003-2004 (13). Thus, many prostate cancer patients are likely to have already been prescribed statins at the time of their cancer diagnosis and treatment.Initial interest in the use of statins in prostate cancer stemmed from epidemiological studies that investigated their chemopreventive properties. Two large case-control series reported a 50%-65% reduction in overall prostate cancer risk among statin users compared with non-users (14, 15

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Antibiotic resistance is a significant threat to human health, with natural products remaining the best source for new antimicrobial compounds. Antimicrobial peptides (AMPs) are natural products with great potential for clinical use as they are small, amenable to customization, and show broad-spectrum activities. Lynronne-1 is a promising AMP identified in the rumen microbiome that shows broad-spectrum activity against pathogens such as methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii. Here we investigated the structure of Lynronne-1 using solution NMR spectroscopy and identified a 13-residue amphipathic helix containing all six cationic residues. We used biophysical approaches to observe folding, membrane partitioning and membrane lysis selective to the presence of anionic lipids. We translated our understanding of Lynronne-1 structure to design peptides which varied in the size of their hydrophobic helical face. These peptides displayed the predicted continuum of membrane-lysis activities in vitro and in vivo, and yielded a new AMP with 4-fold improved activity against A. baumannii and 32-fold improved activity against S. aureus.

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