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Genome-Directed Lead Discovery: Biosynthesis, Structure Elucidation, and Biological Evaluation of Two Families of Polyen...

Schulze, Christopher J Donia, Mohamed S Siqueira-Neto, Jair L Ray, Debalina Raskatov, Jevgenij A Green, Richard E McKerrow, James H Fischbach, Michael A Linington, Roger G

Published in ACS chemical biology

Marine natural products are an important source of lead compounds against many pathogenic targets. Herein, we report the discovery of lobosamides A-C from a marine actinobacterium, Micromonospora sp., representing three new members of a small but growing family of bacterially produced polyene macrolactams. The lobosamides display growth inhibitory ...

Agouti-related protein segments outside of the receptor binding core are required for enhanced short- and long-term feed...

Madonna, Michael E Schurdak, Jennifer Yang, Ying-Kui Benoit, Stephen Millhauser, Glenn L

Published in ACS chemical biology

The agouti-related protein (AgRP) plays a central role in energy balance by reducing signaling through the hypothalamic melanocortin receptors (McRs) 3 and 4, in turn stimulating feeding and decreasing energy expenditure. Mature AgRP(83-132), produced by endoproteolytic processing, contains a central region that folds as an inhibitor cystine knot (...

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