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Venoms: a naturally pre-screened peptide library
Venomous animals such as spiders, molluscs or snakes use their venom to kill or paralyze their prey and/or repel aggressors. Venom is a rich source of bioactive molecules including small molecules, enzymes, and polypeptides. To paralyze prey and predators, peptides have been chosen as part of the process of natural selection, amongst other molecules, to inhibit the nervous system. At a molecular level, this is done by targeting mainly ion channels and GPCRs, which are an important class of membrane receptors involved in signaling pathways. Over the course of millions of years, Nature has selected the most potent peptides to improve venoms’ efficacy. This results both in an optimization of the pharmacological properties of peptides and their pharmacokinetic properties:
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Administration: naturally designed for subcutaneous, intravenous, intramusclar administration after a bite or contact with the venomous animal in question
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Distribution: peptides have to reach their targets after a bite/contact with venom
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Metabolism: peptides need to resist protease degradation and body temperature to be efficient
Regarding safety risks, contrary to popular belief many venom peptides are non-toxic or low in toxicity. Generally, to be considered toxic, a venom needs to be made up of a cocktail of various molecules. Purified peptides are frequently non-toxic or low in toxicity. Furthermore, they demonstrate low levels of immunogenicity with no resulting toxic metabolic intermediates (because peptides are made up of amino-acids).
Applictions of venoms and venom peptides
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Venom as compound libraries |
Venom peptides as drugs |
Venom peptides as tools |
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When used as a compound library for drug-discovery screening programs, venoms are ideal when the target is an ion channel or a GPCR. In a sense, the primary screening process has already been carried out by Nature. Therefore, drug-discovery screening programs using venoms as compound library improve success rates when compared with a chemical library. It is worth noting that only several thousand venoms have so far been screened. Although the venoms screened thus far represent a tiny fraction of those available in Nature, this activity has resulted in hundreds of leads and the successful launch of several new drugs. |
As therapeutic molecules or as structure-based for drug design, venom peptides are particularly interesting. They are generally highly selective for their target and highly potent. Up until now, two venom peptides and several mimetics of venom peptides have already reached the market. Dozens of others are currently in pre-clinical and clinical trials for various indications such as pain, autoimmune diseases, cancer, diabetes, cardiovascular diseases, neurological disorders. |
When used as molecular tools, purified peptides (from 800 to 7000 Da) issued from venom have enabled the pharmacological characterization of a large number of ion channels and other membrane receptors. A large set of purified venom peptides is already available for the characterisation of a significant number of ion channels and for use in other types of research. The discovery of novel venom peptides continues to contribute towards an understanding of the physiological function of orphan targets and enrich their pharmacological classification. |
In each cases, venom peptides have to be synthesized to be obtained in sufficient quantities.
But venom peptides are not just peptides! Most of them naturally contain multiple disulfide-bridges whose properties have tremendous biological value but are also extremely difficult to produce.
Smartox's expertise and understanding of multiple disulfide-bridges and its ability to precisely fold these peptides lies at the heart of its product offering.
Tap into Smartox’s expertise to drive your research forward
Within this context, Smartox specialises in the chemical manufacturing of venom peptides and other kind of cystein-rich peptides. With extensive knowledge acquired in the chemical synthesis of peptides, the solubilization of hydrophobic peptides, the folding of linear peptides, the purification process and analytical techniques, Smartox is able to manufacture complex active peptides ensuring a high purity rate and a high level of reproducibility between batches over short periods of time. Furthermore, this know-how allows us to customize complex peptides with a wide range of options (fluorescent labelling, Qdot, non natural amino-acids, PEG, etc.). Consequently we can offer our clients a catalogue of venom peptides that have been specifically selected for their pharmacological activities as well a range of service offerings.