Argiotoxins represent a class of

polyamine A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. ...

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

s isolated from the

orb-weaver spider Orb-weaver spiders are members of the spider family Araneidae. They are the most common group of builders of spiral wheel-shaped webs often found in gardens, fields, and forests. The English word "orb" can mean "circular", hence the English name ...

(''

Araneus gemma ''Araneus gemma'', commonly known as the cat-faced spider (a name shared with '' Araneus gemmoides''), is a common outdoor orb-weaver spider found in the western United States and Canada. Like most Araneus species, ''A. gemma'' is harmless to h ...

'' and ''

Argiope lobata ''Argiope lobata'' is a species of spider belonging to the family Araneidae. It has a wide distribution encompassing the whole of Africa and stretching to southern Europe and into Asia. The male of this species is small (body length 6 mm) ...

''). The orb-weaver spiders, also known a
araneids
belong to the

Araneidae Orb-weaver spiders are members of the spider family Araneidae. They are the most common group of builders of spiral wheel-shaped webs often found in gardens, fields, and forests. The English word "orb" can mean "circular", hence the English name ...

spider family. This type of spider is found in almost every area of the world. : argiopine

Classification

Argiotoxin can be classified, according to the 1980s classification of spider venoms, as a

of the acylpolyamines family, which contains more than 100 different chemical structures of closely related toxins. Acylpolyamines are neurotoxic compounds that are found only in the venom glands of spiders at a picomolar level. Argiotoxins are classified into three different categories according to its chromophore's nature: the argiopine type, the argiopinine type and the pseudoargiopinine type. * Argiopine: contains 2,4-dihydroxyphenylacetic acid. It is also named Arg-636. * Argiopinines: (4-hydroxyindol-3-yl) acetic acid is carried as the chromophore. These molecules are: Arg-630, Arg-658, Arg-659, Arg-744, Arg-759. * Pseudoargiopinines: They contain a (indol-3-yl) acetic acid. This group is composed of: Arg-373, Arg-728, Arg-743.

Biochemical structure

It is a low-molecular-weight

neurotoxin Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...

which has highly functional polar groups: free phenolic OH and amine and guanidine residues. It also possesses arginine (free NH₂) connected to a -NH (CH)3 NH (C ~) 3NH (CH) 5-NH- one through a

peptide bond In organic chemistry, a peptide bond is an amide type of covalent chemical bond linking two consecutive alpha-amino acids from C1 (carbon number one) of one alpha-amino acid and N2 (nitrogen number two) of another, along a peptide or protein cha ...

polyamine. The polyamine is connected to the asparagine's α-carboxyl group. The amino group of this aminoacid is linked to 2,4-dihydroxyphenyl acetic acid. Its structure was established using spectroscopy 1H, ¹³C-RMN,

mass spectrometry Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is use ...

, and elemental aminoacid analysis. A complete synthesis strategy of argiotoxin and derivatives was developed in order to make biological tests in different living beings. A noted type of argiotoxin, the Arg-636, which molecular formula is C29H52N10O6 has a molecular weight of 636.78658 g/mol. It has a

formal charge In chemistry, a formal charge (F.C. or q), in the covalent view of chemical bonding, is the charge assigned to an atom in a molecule, assuming that electrons in all chemical bonds are shared equally between atoms, regardless of relative electroneg ...

of 0. Its IUPAC name is: (2S) - N- -2- butanediamide

Effects and properties

The effects of argiotoxin, when it enters an organism by a

spider bite A spider bite, also known as arachnidism, is an injury resulting from the bite of a spider. The effects of most bites are not serious. Most bites result in mild symptoms around the area of the bite. Rarely they may produce a necrotic skin wound ...

, are harmless to humans, although in certain cases the bite of argiotoxin spiders can produce mild swelling and itching. Argiotoxin antagonizes the actions of the neurotransmitter glutamate, blocks the functioning of ion channel and affects the synaptic transmission of preys. These toxins, like all the other low-molecular-weight toxins, have a huge potential to be used in neurochemical studies to develop novel drugs of neurotherapeutic applications.

Mechanism of action of argiotoxins

Behaviour of argiotoxins at the junction of nerve and muscle

This spider's venom shows varied action mechanisms that affect the different parts of the nervous impulse transmission chain. As mentioned above, Argiotoxins are

s. This

biomolecular A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include large ...

group can effectively inhibit certain

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

s in the central nervous system of mammals and the insects' glutamic receptor (it has been characterized as an opposite of homomeric and heteromeric glutamate-activated receptor channels ). It has been seen that it can also inhibit the following receptors:

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

NMDA ''N''-methyl--aspartic acid or ''N''-methyl--aspartate (NMDA) is an amino acid derivative that acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor. Unlike ...

(argiotoxin has higher potency at NDMA receptors),

kainate Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...

, and nicotine acetylcholine receptors. It is thought that polyamine toxins' inhibition is both use and voltage dependent. What is more, they bind within the pore of the open channels they inhibit. A lot of attention is drawn to the pharmacological uses of polyamine toxins. They are highly valuable due to their high affinity for

ionotropic glutamate receptors Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate. They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players ...

, important drug targets for

psychiatric disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...

s. It has not been developed yet, although it is thought that it could be a great procedure in

neuroprotection Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...

and in the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. Argiotoxin could even be used as a tool for analyzing the subunit composition of AMPA receptors in native membranes.

Argiotoxin-636

The most relevant example for the strategies mentioned above is the Argiotoxin-636. This is a polyamine toxin isolated from the

's venom. However, there are still some difficulties, as ArgTX-636 cannot distinguish the different subtypes of

. This same toxin is demonstrated to be a good regulator for melanogenesis without cytotoxicity. That's why ArgTX-636 is playing a leading role in the research of cosmetic products against hyper pigmentation. ArgTX-636 can also work as an analgesic due to some peripheral actions. Thanks to its action as inhibitor on gtutamate-activated channels it could work as an anti convulsant.

Experiments with argiotoxins

Argiotoxins studies have been particularly made to discover the relation between inhibition, receptors, and ionic channels. Researchers have specifically pursued the blocking of receptors on invertebrates, rather than on vertebrates. Referring to invertebrates, ''

Planorbarius corneus ''Planorbarius corneus'', common name the great ramshorn, is a relatively large species of air-breathing freshwater snail, an aquatic pulmonate gastropod mollusk in the family Planorbidae, the ram's horn snails, or planorbids, which all have ...

'' is a mollusc involved in one of the many ionic experiments. To begin with, neurons of molluscan pedal ganglia were isolated and transferred to a special chamber with saline solution and regulated temperature. Then, the observation was based on routine

voltage clamp The voltage clamp is an experimental method used by electrophysiologists to measure the ion currents through the membranes of excitable cells, such as neurons, while holding the membrane voltage at a set level. A basic voltage clamp will iterativ ...

technique. Electrical measurements were obtained from the evaluation of neurons response to various substances (argiopines). In addition to that,

crayfish Crayfish are freshwater crustaceans belonging to the clade Astacidea, which also contains lobsters. In some locations, they are also known as crawfish, craydids, crawdaddies, crawdads, freshwater lobsters, mountain lobsters, rock lobsters, mu ...

, a freshwater crustacean, has followed a similar protocol to this study. In this case, the analysis was made of the stomach muscles and using the

patch clamp The patch clamp technique is a laboratory technique in electrophysiology used to study ionic currents in individual isolated living cells, tissue sections, or patches of cell membrane. The technique is especially useful in the study of excitabl ...

technique. The research findings were obtained taking into account the bursts of openings of excitatory channels. Other experiments use spectroscopy in order to analyse and differentiate these molecules.

HPLC High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pa ...

, mass spectrometry, UV data and amino acid analysis are the elements that allow identifying diverse argiotoxins due to their spectrum. ''

'' toxins (Arg 636, Arg 630, Arg 658, Arg 744, Arg 759, Arg 373, Arg 728, Arg 723, ...) show a close similarity in their structures; the subtle differences between them are chemical points, such as N-methyl groups, molecular masses or lysine residues that are determined in a certain position in their structure.

References

External links

*{{Commonscatinline Spider toxins Amides Guanidines Phenols Polyamines