Chemical and Functional Characterization 
of Scorpion Toxins 
Lourival Domingos Possani, Ph.D. — International Research Scholar 
Dr. Possani is Professor and Chairman of the Department of Biochemistry at the Biotechnology Institute, 
National Autonomous University of Mexico, Cuernavaca. He received his B.S. degree in natural history 
from the Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, and his Ph.D. degree in 
molecular biophysics from the University of Paris, France. He completed the academic requirements for 
his Ph.D. degree in biochemistry at the Rockefeller University, working with Edward Reich on the isolation 
of the acetylcholine receptor. 
SCORPIONISM is a serious public health prob- 
lem in certain areas of the world. In Mexico 
alone, more than 200,000 people are stung by 
scorpions each year. Thanks to serotherapy with 
horse antisera, the number of deaths is kept to 
approximately 700-800 annually. Not all scor- 
pions are dangerous to humans. Among the 136 
species known to live in Mexico, only 6 present a 
real risk. They belong to the family Buthidae, 
genus Centruroides. The species dangerous to 
humans are Centruroides elegans, C. infamatus 
infamatus, C. limpidus limpidus, C. limpidus 
tecomanus, C. noxius, C. sculpturatus (which 
occurs also in Arizona), and C. suffusus suffusus. 
Half of the casualties are due to one species, 
represented by two subspecies: C. limpidus lim- 
pidus from the states of Guerrero and Morelos, 
and C. limpidus tecomanus from the state of Co- 
lima. All dangerous species abide in the Pacific 
coast region. No dangerous scorpions are found 
in the Gulf of Mexico region, the Yucatan Penin- 
sula, or Mexico City. 
Envenomation by the sting of these arachnids is 
due to low-molecular-weight peptides called 
toxins. More than 1 00 such toxins have been puri- 
fied and characterized. There are three well- 
known classes of scorpion toxins: short-chain 
peptides (38-39 amino acid residues long), 
which are K"^ channel blockers; medium-chain 
peptides (61-66 amino acid residues), specific 
for Na^ channels; and long-chain peptides (about 
70 amino acid residues), toxic to insects and 
crustaceans. Recently a fourth class seems to have 
emerged with the discovery of low-molecular- 
weight proteins (about 1 20 amino acid residues) 
that affect the Ca^^ release channel from sarco- 
plasmic reticulum. 
The study of scorpion toxins is scientifically, 
medically, and biotechnologically interesting. 
They represent several families of structurally re- 
lated polypeptides with exquisite preference for 
ion channel molecules, which makes them a 
model for future new drugs to control cell excit- 
ability or for new types of specific insecticides. 
And they represent excellent tools for studying 
cellular responses, permitting discrimination 
among receptor molecules in the membranes and 
investigation of various types of ion channels. 
The contribution of our research group, which 
comprises a multidisciplinary interaction with 
investigators from several countries, began with 
the isolation and chemical characterization of 
toxin gamma, a potent Na^ channel blocker, from 
the Brazilian scorpion Tityus serrulatus. Our 
work was extended at the beginning of the 1 980s 
by the discovery of the first peptide capable of 
blocking the delayed rectifier channel from 
the squid axon. It is a short-chain peptide (39 
amino acid residues) and was subsequently 
shown to affect other types of channels. This 
peptide was named noxiustoxin, after the scor- 
pion C. noxius. 
Our studies continued with the purification 
and characterization of more than 25 different 
peptides from scorpion venoms, specific block- 
ers of Na^ channels from a variety of different 
tissues. At least eight additional small-chain pep- 
tides similar to noxiustoxin were also isolated 
and characterized. To study the function of these 
toxins, we used neurotransmitter-release and 
-binding studies with brain synaptosomes and 
mainly electrophysiological studies with a vari- 
ety of excitable cells. Our more recent progress 
in this field is focused on the three lines of re- 
search mentioned below. 
Chemical Synthesis of Peptides 
and Monoclonal Antibodies 
We have recently synthesized, by the solid- 
phase method of Merrifield, more than 1 00 dif- 
ferent peptides corresponding to segments of the 
amino acid sequence of the scorpion toxins. 
These peptides and the preparation of a dozen 
distinct monoclonal antibodies allowed us to 
probe for specific structural regions of the toxins. 
For example, the nonapeptide at the amino-ter- 
minal region of noxiustoxin was shown to recog- 
nize and affect channels in a manner similar to 
the native peptide. These results are promising in 
the context of possible development of new 
drugs aimed at controlling cellular excitability 
through channels. 
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