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Structural determination of nanomolar quantities of neuroactive peptides by nuclear magnetic resonance

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Date Issued:
2005
Summary:
The specificity of the conotoxin is one of the attributes that make them a valuable diagnostic tool in the characterization of neuronal mechanisms, or therapeutic agents in medicine. It appears that Nature has provided us with a pharmaceutical tool in the form of Conus peptides. Further studies will only enhance our understanding, and use, of these molecules in medicine and science. The study of three-dimensional structure in relation to the function of cone snail peptides is an area of increasing interest. The venom of a single cone snail can contain as many as 300 different chemical components. Individual cone snail venom components, or conopeptides, can have powerful neurological effects. For many interesting species, not enough venom collected from the natural origin is available for experimental investigations. After a laborious separation procedure, only nanomole quantities of these native conopeptides are able to be obtained. Therefore, several experimental applications, such as NMR spectroscopy, are difficult to carry out using traditional methods. The research was focused on using nanoNMR spectroscopy as an alternative method to the conventional NMR spectroscopy method in order to analyze small quantities of novel peptides with unknown three-dimensional conformational arrangement. The experimental results obtained using the HR-MAS NMR technique, in addition to the use of a 3mm gHCN (with 1.7mm inserts) NMR probes, proved the capability of conformational analysis of different types of natural products at sample levels down to nanomole range. Understanding the interaction between agonist or antagonist ligands and their target receptors, at a molecular level, offer promise for the development of pharmacological therapeutics for the central nervous system. Conopeptides are of great interest as ligands in neuroscience and are valuable leads in drug design, based on their specificity and potency for therapeutically relevant receptors and ion channels. For instance, the compound called Prialt (formerly known as Ziconotide), a synthetic form of a cone snail-derived peptide, is the most powerful painkiller known and has already received the Food and Drug Administration (FDA) approval. The drug is part of a new class known as the N-type calcium channel blockers, which are responsible for transmitting pain signals. Several related cone snail drugs are currently in clinical trials and could eventually be used to treat different diseases such as Alzheimer's, epilepsy and Parkinson's.
Title: Structural determination of nanomolar quantities of neuroactive peptides by nuclear magnetic resonance.
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Name(s): Matei, Elena
Florida Atlantic University, Degree Grantor
Charles E. Schmidt College of Science
Department of Chemistry and Biochemistry
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Issuance: monographic
Date Issued: 2005
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 114 p.
Language(s): English
Summary: The specificity of the conotoxin is one of the attributes that make them a valuable diagnostic tool in the characterization of neuronal mechanisms, or therapeutic agents in medicine. It appears that Nature has provided us with a pharmaceutical tool in the form of Conus peptides. Further studies will only enhance our understanding, and use, of these molecules in medicine and science. The study of three-dimensional structure in relation to the function of cone snail peptides is an area of increasing interest. The venom of a single cone snail can contain as many as 300 different chemical components. Individual cone snail venom components, or conopeptides, can have powerful neurological effects. For many interesting species, not enough venom collected from the natural origin is available for experimental investigations. After a laborious separation procedure, only nanomole quantities of these native conopeptides are able to be obtained. Therefore, several experimental applications, such as NMR spectroscopy, are difficult to carry out using traditional methods. The research was focused on using nanoNMR spectroscopy as an alternative method to the conventional NMR spectroscopy method in order to analyze small quantities of novel peptides with unknown three-dimensional conformational arrangement. The experimental results obtained using the HR-MAS NMR technique, in addition to the use of a 3mm gHCN (with 1.7mm inserts) NMR probes, proved the capability of conformational analysis of different types of natural products at sample levels down to nanomole range. Understanding the interaction between agonist or antagonist ligands and their target receptors, at a molecular level, offer promise for the development of pharmacological therapeutics for the central nervous system. Conopeptides are of great interest as ligands in neuroscience and are valuable leads in drug design, based on their specificity and potency for therapeutically relevant receptors and ion channels. For instance, the compound called Prialt (formerly known as Ziconotide), a synthetic form of a cone snail-derived peptide, is the most powerful painkiller known and has already received the Food and Drug Administration (FDA) approval. The drug is part of a new class known as the N-type calcium channel blockers, which are responsible for transmitting pain signals. Several related cone snail drugs are currently in clinical trials and could eventually be used to treat different diseases such as Alzheimer's, epilepsy and Parkinson's.
Identifier: 9780542271687 (isbn), 12162 (digitool), FADT12162 (IID), fau:9069 (fedora)
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Adviser: Frank Mari.
Thesis (Ph.D.)--Florida Atlantic University, 2005.
Subject(s): Physics, General
Biophysics, General
Held by: Florida Atlantic University Libraries
Persistent Link to This Record: http://purl.flvc.org/fcla/dt/12162
Sublocation: Digital Library
Use and Reproduction: Copyright © is held by the author, with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Use and Reproduction: http://rightsstatements.org/vocab/InC/1.0/
Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.