Abstract Title
Identifying the Unknown: Isolation and Characterization of Novel Alkaloids in Veratrum californicum
Additional Funding Sources
The project described was supported by Institutional Development Awards (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under Grant Nos. P20GM103408 and P20GM109095. We also acknowledge support from Lewis-Clark State University and The Biomolecular Research Center at Boise State with funding from the National Science Foundation, Grant Nos. 0619793 and 0923535, the MJ Murdock Charitable Trust, and the Idaho State Board of Education.
Abstract
In the 1950s, Idaho sheepherders observed abnormally high rates of lambs born with craniofacial deformity, referred to as cyclopia. The birth defects were attributed to ingestion of Veratrum californicum. The steroidal alkaloid in V. californicum determined to be the causative agent was cyclopamine. The mechanism of action of cyclopamine is to inhibit the hedgehog (hh) cell signaling pathway. Extraction of dried and ground V. californicum root and rhizome by ethanol yields at least 14 different steroidal alkaloids, of which only eight have been identified and characterized. The six alkaloids that remain to be identified demonstrate hh cell signaling pathway inhibition. Here we present the isolation and characterization of one of the six unknown alkaloids, using high pressure liquid chromatography, nuclear magnetic resonance spectroscopy, mass spectrometry, and circular dichroism spectropolarimetry.
Identifying the Unknown: Isolation and Characterization of Novel Alkaloids in Veratrum californicum
In the 1950s, Idaho sheepherders observed abnormally high rates of lambs born with craniofacial deformity, referred to as cyclopia. The birth defects were attributed to ingestion of Veratrum californicum. The steroidal alkaloid in V. californicum determined to be the causative agent was cyclopamine. The mechanism of action of cyclopamine is to inhibit the hedgehog (hh) cell signaling pathway. Extraction of dried and ground V. californicum root and rhizome by ethanol yields at least 14 different steroidal alkaloids, of which only eight have been identified and characterized. The six alkaloids that remain to be identified demonstrate hh cell signaling pathway inhibition. Here we present the isolation and characterization of one of the six unknown alkaloids, using high pressure liquid chromatography, nuclear magnetic resonance spectroscopy, mass spectrometry, and circular dichroism spectropolarimetry.
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