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Broad Application of Conotoxins As Molecular Probes, Therapeutic Leads and Drug Delivery Vectors In Excitable and Non-Excitable Systems
- Date Issued:
- 2019
- Abstract/Description:
- Conotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus, which effectively treats patients suffering from severe chronic pain without consequent narcotic effects. Additionally, six other conotoxins have reached clinical trials and many novel ones are being discovered every day. Investigations reported in this dissertation broadens the applicability of conotoxins to non-excitable systems. Here, conotoxins from the dissected venom of the vermivorous cone snail Conus nux were isolated and purified by size exclusion and reverse phase HPLC and characterized by MALDI-TOF and MS/MS spectrometry. The purified conopeptide fractions revealed: 1) antagonist activity of conotoxin NuxVID on two human voltage-gated sodium channels, displaying capabilities as a practical molecular probe and a potential therapeutic lead. 2) Ability for two novel conotoxins to traverse artificial biological membranes, suggesting their potential as drug delivery systems. 3) In vitro capacity of several novel conopeptides to interfere with the adhesion of PfEMP1 domains, expressed in P. falciparum infected erythrocytes, to vascular endothelial and placenta receptors. Lastly, this work reveals binding of the synthetic form of α-conotoxin ImI, from the vermivorous cone snail Conus imperialis, to the α7 nAChR of macrophage-like-cells derived from the pre-monocytic leukemic cell line THP-1 in support of the involvement of this receptor in the cholinergic anti-inflammatory pathway.
Title: | Broad Application of Conotoxins As Molecular Probes, Therapeutic Leads and Drug Delivery Vectors In Excitable and Non-Excitable Systems. |
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Name(s): |
Padilla, Alberto, author Hartmann, James X., Thesis advisor Mari, Frank, Thesis advisor Florida Atlantic University, Degree grantor Charles E. Schmidt College of Science Department of Biological Sciences |
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Type of Resource: | text | |
Genre: | Electronic Thesis Or Dissertation | |
Date Created: | 2019 | |
Date Issued: | 2019 | |
Publisher: | Florida Atlantic University | |
Place of Publication: | Boca Raton, Fla. | |
Physical Form: | application/pdf | |
Extent: | 141 p. | |
Language(s): | English | |
Abstract/Description: | Conotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus, which effectively treats patients suffering from severe chronic pain without consequent narcotic effects. Additionally, six other conotoxins have reached clinical trials and many novel ones are being discovered every day. Investigations reported in this dissertation broadens the applicability of conotoxins to non-excitable systems. Here, conotoxins from the dissected venom of the vermivorous cone snail Conus nux were isolated and purified by size exclusion and reverse phase HPLC and characterized by MALDI-TOF and MS/MS spectrometry. The purified conopeptide fractions revealed: 1) antagonist activity of conotoxin NuxVID on two human voltage-gated sodium channels, displaying capabilities as a practical molecular probe and a potential therapeutic lead. 2) Ability for two novel conotoxins to traverse artificial biological membranes, suggesting their potential as drug delivery systems. 3) In vitro capacity of several novel conopeptides to interfere with the adhesion of PfEMP1 domains, expressed in P. falciparum infected erythrocytes, to vascular endothelial and placenta receptors. Lastly, this work reveals binding of the synthetic form of α-conotoxin ImI, from the vermivorous cone snail Conus imperialis, to the α7 nAChR of macrophage-like-cells derived from the pre-monocytic leukemic cell line THP-1 in support of the involvement of this receptor in the cholinergic anti-inflammatory pathway. | |
Identifier: | FA00013250 (IID) | |
Degree granted: | Dissertation (Ph.D.)--Florida Atlantic University, 2019. | |
Collection: | FAU Electronic Theses and Dissertations Collection | |
Note(s): | Includes bibliography. | |
Subject(s): |
Conotoxins Drug Delivery Systems Molecular Probes |
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Held by: | Florida Atlantic University Libraries | |
Sublocation: | Digital Library | |
Persistent Link to This Record: | http://purl.flvc.org/fau/fd/FA00013250 | |
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. |