Conformational behavior of the linear hexapeptide senktide: A receptor specific tachykinin analog

AbstractA receptor selective linear hexapeptide tachykinin analog, senktide, is shown to be highly ordered in solution. The conformational restriction is attributed to steric and electrostatic interactions produced by N-methylation of the third amino acid residue in the sequence and the negatively charged N-terminus. The structure of senktide is described as a dynamic mixture of similar conformations where the predominant one is a distorted antiparallel hydrogen bonded β-pleated sheet. The observed senktide-receptor specificity is suggested to result from a selection of this or a closely related conformation

Obesity Increases Mortality and Modulates the Lung Metabolome during Pandemic H1N1 Influenza Virus Infection in Mice

Obese individuals are at greater risk for hospitalization and death from infection with the 2009 pandemic H1N1 influenza virus (pH1N1). In this study, diet-induced and genetic-induced obese mouse models were utilized to uncover potential mechanisms by which obesity increases pH1N1 severity. High fat diet-induced and genetic-induced obese mice exhibited greater pH1N1 mortality, lung inflammatory responses and excess lung damage despite similar levels of viral burden compared with lean control mice. Further, obese mice had fewer bronchoalveolar macrophages and regulatory T cells during infection. Obesity is inherently a metabolic disease, and metabolic profiling has found widespread usage in metabolic and infectious disease models for identifying biomarkers and enhancing understanding of complex mechanisms of disease. To further characterize the consequences of obesity on pH1N1 infection responses, we performed global liquid chromatography-mass spectrometry metabolic profiling of lung tissue and urine. An array of metabolites were perturbed by obesity both prior to and during infection. Uncovered metabolic signatures were used to identify changes in metabolic pathways that were differentially altered in the lungs of obese mice such as fatty acid, phospholipid, and nucleotide metabolism. Taken together, obesity induces distinct alterations in the lung metabolome, perhaps contributing to aberrant pH1N1 immune responses