Natural and Selected Synthetic Toxins. Biological Implications

423 Pages·2000·42.01 MB·English

by  Anthony T. Tu and William Gaffield (Eds.)

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In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
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In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
ACS SYMPOSIUM SERIES 745
Natural and Selected Synthetic
Toxins
Biological Implications
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American Chemical Society, Washington, DC
American Chemical Society
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In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
RA 1191 .N38 2000 c.1
Natural and selected
synthetic toxins
Library of Congress C
Natural and selected synthetic toxins : biological implications / [editors] Anthony T. Tu, William
Gaffield.
p. cm.—(ACS symposium series , ISSN 0097-6156 ; 745)
Includes bibliographical references and index.
ISBN 0-8412-3630-5
g 1 1. Toxins—Congresses.
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In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Foreword
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In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Preface
The chapters comprising this American Chemical Society (ACS) Series volume
are derived from presentations at the Third International Symposium on Natural
Toxins, which was convened at the 216th National Meeting of the ACS in
Boston, Massachusetts, August 23-27,1998. The Symposium was sponsored by
the Division of Agricultural and Food Chemistry and contained presentations
from 26 scientists who represented 11 countries on four continents.
A common characteristic of natural toxins is that minute quantities exert a
pronounced deleterious effect on the metabolic and physiologic functions of a
living organism. Because natural toxins usually express highly specific and po­
tent effects, they often serve as excellent candidates from which therapeutic
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ANTHONY T. TU
Department of Biochmistry and Molecular Biology
Colorado State University
Fort Collins, CO 80525
WILLIAM GAFFIELD
Research Chemist
Western Regional Research Center
U.S. Department of Agriculture
Albany, CA 94710
xi
In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Chapter 1
Structure-Function Relations of Natural Toxins
and Nerve Agents: An Overview
Anthony T. Tu1 and William Gaffield2
1Department of Biochemistry and Molecular Biology,
Colorado State University, Fort Collins, CO 80523-1870
2Western Regional Research Center, U.S. Department of Agriculture,
s.org h001 Albany, CA 94710
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12 | http://pubs.a1/bk-2000-0745. Nature has endowed mankind with sources of an extraordinarily rich array of complex
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md creation of diverse collections of chemical structures followed by critical selection of
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2.34 ber 2 biological processes are elaborated and understood, the insights gleaned, as well as the
5m processes themselves, can be combined with the tools of the physical and biological
66.1ece sciences to create new and novel molecules that incorporate functions found neither in
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fungal and marine organisms; however, the potential for the discovery of new natural
products is far from exhausted and compounds of natural origin continue to represent a
key source for the discovery of important leads. Furthermore, although combinatorial
chemistry and high-throughput screening are the methods of choice for lead-structure
optimization, a combinatorial library will not provide the structural diversity inherent in
a library generated from natural products.
As an example, natural products possessing physiological properties such as
those of constituents of snake, spider, and scorpion venoms, can assist in creating
targeted libraries of potential drug candidates (3). Venom peptides and proteins that act
©2000 American Chemical Society 1
In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
2
upon mammalian physiological processes are extremely site-specific in their actions and
this specificity is highly valuable in performing as a lead therapeutic or biological probe.
Thus, although a protein isolated and purified from snake venom might be
therapeutically useful, more likely it will serve as a lead for drug development.
Alternatively, a venom protein can function as a biological probe that delineates the
molecular surface of its receptor binding site, thus providing key insights that enable the
design and development of simpler molecules that mimic the desired receptor site and
have the potential to serve as drugs.
The biological implications of natural toxins that are derived from marine, fungal,
microbial, plant, and animal sources, along with selected synthetic nerve gases and
g 1 doping agents, are described in this ACS Symposium Series volume under four subject
s.orh00 headings (for earlier natural toxin symposia, see ref. 4,5). Although the nerve gases and
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2.34 ber 2 Palythoa genus contain palytoxin, a toxin that depolarizes excitable tissue and ruptures
5m blood cells. Extracts from these corals were employed by natives of the Hawaiian
66.1ece Islands for hunting and warfare; however, the relative inaccessibility of marine
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eo marine organisms, both toxic and benign. T. Higa (Japan) describes the isolation and
wnloadblicati characterization of numerous cytotoxic and bioactive compounds from coral reef
Do Pu sponges that are prime candidates for anti-tumor drugs and immunostimulatory
compounds. Pardaxin is a unique substance released from a Red Sea flatfish that repels
a predatory shark. P.H. Lazarovici (Israel) reports the cellular and molecular
mechanism of pardaxin effects on cellular signaling.
Serious contamination of foodstuffs often results from exposure to fungi and
their constituent mycotoxins. A notorious example is the fungus Claviceps purpurea
that produces ergot alkaloids which can contaminate rye and other cereal grains resulting
in induction of ergotism in consumers. Other fimgal toxins are more insidious, inducing
liver or gastrointestinal tumors over a period of years. Prominent among the latter
toxins are the aflatoxins which were originally identified in 1960 following the deaths of
thousands of turkeys. No direct evidence exists that liver disease in humans can be
caused by ingestion of aflatoxins although a high incidence of liver cancer has occurred in
In Natural and Selected Synthetic Toxins; Tu, A., et al.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.