Bioactive Mimetics of Conotoxins and other Venom Peptides

Duggan, Peter J.; Tuck, Kellie L.

doi:10.3390/toxins7104175

Cited by 27 publications

(22 citation statements)

References 88 publications

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“…Therefore, blockers of these channels would be expected to produce antinociceptive effects by reducing transmitter release. For example, ziconitide, a peptide Ca V 2.2 blocker obtained from a Cone snail, has been shown to be effective in several chronic pain conditions [37]. It has been suggested that VGCCs are important for mechanical excitability of slowly conducting afferents innervating the rat knee [38].…”

Section: Ion Channelsmentioning

confidence: 99%

Emerging Targets for the Management of Osteoarthritis Pain

Malfait

Miller

2016

Curr Osteoporos Rep

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Worldwide, osteoarthritis (OA) is one of the leading causes of chronic pain, for which adequate relief is not available. Ongoing peripheral input from the affected joint is a major factor in OA-associated pain. Therefore, this review focuses predominantly on peripheral targets emerging in the preclinical and clinical arena. Nerve growth factor is the most advanced of these targets, and its blockade has shown tremendous promise in clinical trials in knee OA. A number of different types of ion channels, including voltage-gated sodium channels and calcium channels, transient receptor potential channels and acid-sensing ion channels, are important for neuronal excitability and play a role in pain genesis. Few channel blockers have been tested in preclinical models of OA, with varying results. Finally, we discuss some examples of G-protein coupled receptors, which may offer attractive therapeutic strategies for OA pain, including receptors for bradykinin, calcitonin gene-related peptide, and chemokines. Since many of the pathways described above can be selectively and potently targeted, they offer an exciting opportunity for pain management in OA, either systemically or locally.

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Section: Ion Channelsmentioning

confidence: 99%

Emerging Targets for the Management of Osteoarthritis Pain

Malfait

Miller

2016

Curr Osteoporos Rep

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“…Multiple reports suggested that non-peptide analogues of ω-conotoxins may target Ca v 2.2 channels [38] , [41] , [43] , [70] , [83] , [84] , [85] . These non-peptide conotoxin mimetics mimic the scaffolds of ω-conotoxin MVIIA, CVID and GVIA [62] . In total, out of 30 docked compounds ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Purposefully, the mimicry of venom peptides may hold a considerable promise due to lack of detailed structural information of neuronal ion channel. The non-peptide mimetics of MVIIA and GVIA ω-conotoxins isolated from marine cone snail efficiently bind to neuronal Ca 2+ channels at low concentrations [9] , [62] . Here in this study, out of 30 known non-peptide analogues of ω-conotoxins ( Table S1 , Fig.…”

Section: Discussionmentioning

confidence: 99%

Conformational ensembles of non-peptide ω-conotoxin mimetics and Ca+2 ion binding to human voltage-gated N-type calcium channel Cav2.2

Sameera

Shah

Rashid

2020

Computational and Structural Biotechnology Journal

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“…Chlorotoxin from the venom of the scorpion Leiurus quinquestriatus, has been chemically conjugated to a dye and used as 'tumour paint' because the toxin serendipitously binds selectively to neuronal cancer cells by providing a clear demarcation between cancerous and normal tissue [41]. Peptide toxins can also be structurally modified to provide peptidomimetics incorporating functionality (e.g., conformational constraints, non-native amino acids) to overcome some of their physicochemical limitations, including plasma instability and cell permeability, therefore increasing their overall range of applications within the laboratory [42].…”

Section: Ion Channels and The Nervous Systemmentioning

confidence: 99%

Friends or Foes? Emerging Impacts of Biological Toxins

Clark

Casewell

Elliott

et al. 2019

Trends in Biochemical Sciences

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Toxins are substances produced from biological sources (e.g., animal, plants, microorganisms) that have deleterious effects on a living organism. Despite the obvious health concerns of being exposed to toxins, they are having substantial positive impacts in a number of industrial sectors. Several toxin-derived products are approved for clinical, veterinary, or agrochemical uses. This review sets out the case for toxins as 'friends' that are providing the basis of novel medicines, insecticides, and even nucleic acid sequencing technologies. We also discuss emerging toxins ('foes') that are becoming increasingly prevalent in a range of contexts through climate change and the globalisation of food supply chains and that ultimately pose a risk to health. Toxins and Toxinology In the natural world, toxins are employed for diverse purposes, from the prey-incapacitating molecules found in snake, spider, and cone snail venom, to the defensive compounds harboured by numerous poisonous plant and animal species. While the consequences of human intoxication can be severe (Box 1), the functional diversity of biological toxins has led to their frequent use as experimental tools for studying physiological and pharmacological mechanisms (e.g., synaptic transmission, ion channel subtypes) (Figure 1). Toxinology involves the identification, characterisation, production, and engineering of biological toxins along with their application or repurposing as research tools and clinical products. As such, toxinology encompasses the study of the evolution, chemistry, biology, and clinical effects of toxins and includes potential biotechnological and/or therapeutic applications. Experimental applications of toxins as tools for physiologists go back a long time, including Claude Bernard's experiments in the 1800s with curare to demonstrate the existence of chemical signalling between nerves and muscles [2], and Henry Dale's use of muscarine and nicotine to show different subtypes of receptors for acetylcholine [3]. Snake toxins were critical for the first isolation of a receptor for a neurotransmitter [a-bungarotoxin and nicotinic acetylcholine receptors (nAChRs)] [4]. Recently, peptide toxins have been very useful in teasing out the functional importance of different subtypes of ion channels that are critical for neuronal function and cellular signalling [5-7]. An increasing number of toxins are now transitioning from the laboratory to the clinic and the balance of research in this aspect of toxinology is shifting from the classical development of anti-toxins and anti-venoms towards drug discovery [8,9]. The attraction of toxins for drug discovery lies in their often unique selectivity of their biological effects coupled with high potency. Toxic plant alkaloids were the first source of toxin-derived therapeutics, notably

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Bioactive Mimetics of Conotoxins and other Venom Peptides

Cited by 27 publications

References 88 publications

Emerging Targets for the Management of Osteoarthritis Pain

Emerging Targets for the Management of Osteoarthritis Pain

Conformational ensembles of non-peptide ω-conotoxin mimetics and Ca+2 ion binding to human voltage-gated N-type calcium channel Cav2.2

Friends or Foes? Emerging Impacts of Biological Toxins

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