Journal ArticleDOI
Two new classes of conopeptides inhibit the alpha1-adrenoceptor and noradrenaline transporter.
Iain A. Sharpe,John Gehrmann,Marion L. Loughnan,Linda Thomas,Denise A. Adams,Ann Atkins,Elka Palant,David J. Craik,David J. Adams,Paul F. Alewood,Richard J. Lewis +10 more
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Two new classes of conopeptides are discovered that act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugs.Abstract:
Cone snails use venom containing a cocktail of peptides ('conopeptides') to capture their prey. Many of these peptides also target mammalian receptors, often with exquisite selectivity. Here we report the discovery of two new classes of conopeptides. One class targets alpha1-adrenoceptors (rho-TIA from the fish-hunting Conus tulipa), and the second class targets the neuronal noradrenaline transporter (chi-MrIA and chi-MrIB from the mollusk-hunting C. marmoreus). rho-TIA and chi-MrIA selectively modulate these important membrane-bound proteins. Both peptides act as reversible non-competitive inhibitors and provide alternative avenues for the identification of inhibitor drugsread more
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Natural products to drugs: natural product derived compounds in clinical trials
Mark S. Butler,Mark S. Butler +1 more
TL;DR: Natural product and natural product-derived compounds that are being evaluated in clinical trials or are in registration (as at 31st December 2007) have been reviewed, as well as natural products for which clinical trials have been halted or discontinued since 2005.
Journal ArticleDOI
Conus venoms: a rich source of novel ion channel-targeted peptides.
TL;DR: This review focuses on the targeting specificity of conotoxins and their differential binding to different states of an ion channel.
Journal ArticleDOI
Natural products: an evolving role in future drug discovery.
Bhuwan B. Mishra,Vinod K. Tiwari +1 more
TL;DR: The present review describes natural products, semi-synthetic NPs and NP-derived compounds that have undergone clinical evaluation or registration from 2005 to 2010 by disease area i.e. infectious, immunological, cardiovascular, neurological, inflammatory and related diseases and oncology.
Journal ArticleDOI
SLC6 Neurotransmitter Transporters: Structure, Function, and Regulation
Anders S. Kristensen,Jacob Andersen,Trine Nygaard Jørgensen,Lena Sørensen,Jacob Eriksen,Claus J. Loland,Kristian Strømgaard,Ulrik Gether +7 more
TL;DR: The understanding of the molecular structure, function, and pharmacology of these proteins has advanced rapidly, and intensive efforts have been directed toward understanding the molecular and cellular mechanisms involved in regulation of the activity of this important class of transporters, leading to new methodological developments and important insights.
Journal ArticleDOI
Therapeutic potential of venom peptides
Richard J. Lewis,Maria L. Garcia +1 more
TL;DR: The pharmacology of venom peptides is surveyed and their therapeutic prospects are assessed for the treatment of pain, diabetes, multiple sclerosis and cardiovascular diseases are assessed.
References
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Pharmacologic analysis of drug-receptor interaction
TL;DR: In this paper, a statistical assessment of biological significance from data affinity efficacy competitive antagonism allotopic, noncompetitive, and irreversible antagonism methods of drug and receptor classification is presented.
Journal ArticleDOI
Diversity of Conus neuropeptides
Baldomero M. Olivera,Jean Rivier,Craig Clark,Cecilia A. Ramilo,Gloria P. Corpuz,Fe C. Abogadie,E. Edward Mena,Scott Woodward,David R. Hillyard,Lourdes J. Cruz +9 more
TL;DR: It now seems that the Conus species will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be ultimately comparable to that of plant alkaloids or secondary metabolites of microorganisms.
Journal ArticleDOI
Purification and sequence of a presynaptic peptide toxin from Conus geographus venom.
TL;DR: A novel toxin, omega-conotoxin (omega-CgTX), from the venom of the fish-eating marine mollusc Conus geographus has been purified and biochemically characterized, providing a potentially powerful probe for exploring the vertebrate presynaptic terminal.
Journal ArticleDOI
Pharmacological evidence that adenosine triphosphate and noradrenaline are co-transmitters in the guinea-pig vas deferens.
Peter Sneddon,David P. Westfall +1 more
TL;DR: The results suggest that the first phase of the neurogenic contractile response of the vas deferens and the e.j.p.s. are mediated by ATP acting on P2‐purinoreceptors, whereas NA mediates phase two, via alpha 1‐adrenoceptors.
Journal ArticleDOI
Conus geographus toxins that discriminate between neuronal and muscle sodium channels.
Lourdes J. Cruz,William R. Gray,Baldomero M. Olivera,R D Zeikus,Lynne M. Kerr,Doju Yoshikami,Edward Moczydlowski +6 more
TL;DR: Using the major peptide (GIIIA) in electrophysiological studies on nerve-muscle preparations and in single channel studies using planar lipid bilayers, it is established that the toxin blocks muscle sodium channels, while having no discernible effect on nerve or brain sodium channels.