Font Size: a A A

Characterization of neuromodulatory and neurotoxic marine natural products using microseparations, NMR and mass spectrometry

Posted on:2003-08-17Degree:Ph.DType:Dissertation
University:University of Illinois at Urbana-ChampaignCandidate:Kelley, Wayne PFull Text:PDF
GTID:1461390011489073Subject:Chemistry
Abstract/Summary:
The task of unraveling communication and functioning within a central nervous system (CNS) is certainly a daunting technical challenge. In humans, the CNS may be comprised of 1012 neurons that have a latent and synergistic form and function. The use of less complex nervous systems to investigate simple, well-defined behaviors gives an opportunity to elucidate the molecular role that specific compounds have to initiate, alter or block neural communication and functioning.; This dissertation work details a number of analytical techniques and methods that have been employed in order to examine the role of chemical messengers, signaling molecules and neurotoxins from the relatively simple, well-defined, systems of marine invertebrates. Many of the samples require the handling of minimal volumes and may contain scarce or precious amounts of analyte obscured within complex matrices. To this end, techniques have been developed for the investigation of mass- or volume-limited tissues or extracts, to probe for signaling/modulating molecules with spatial, chemical and temporal specificity. Liquid microseparations, nuclear magnetic resonance (NMR) and mass spectrometry (MS) have been utilized to characterize chemical messengers and signaling molecules that can initiate, modify and suppress neuronal communication and affect discrete functioning and behavior.; Matrix-assisted laser desorption/ionization (MALDI) with time-of-flight mass spectrometry (TOF MS), electrospray ionization (ESI) ion trap MS and nanospray ionization (NSI) mass spectrometry allow for rapid and sensitive screening of natural product analytes. Additionally, MALDI-TOF MS allows for the assay of limited amounts of sample with high sensitivity and mass accuracy. Tissues and analyte containing substrates can be examined as well as cellular homogenates. The ESI ion trap MS instrument, in conjunction with online separations, allows for rapid screening of liquid extracts and homogenates and, in one concerted step, can achieve robust and highly sensitive structural characterization by collisionally induced dissociation (CID).; A number of different neuromodulatory compounds from marine species are examined including toxins from venomous cone snails. Conotoxins represent a wealth of neuropharmacologically active peptides as well as tools for basic research and a review of cone snails and their toxins is included.
Keywords/Search Tags:Mass spectrometry, Marine
Related items