The Biological and Biophysical Properties of the Spider Peptide Gomesin

Tanner, John Douglas; Deplazes, Evelyne; Mancera, Ricardo L.

doi:10.3390/molecules23071733

Cited by 19 publications

(24 citation statements)

References 55 publications

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“…Gomesin (Gm), derived from a Brazilian spider, (Acanthoscurria gomesiana) has demonstrated to have anti-cancer activity in vitro against a broad range of murine and human cancer cell lines, including melanoma and leukemia derived cell lines [ 128 ]. The mechanism involves the interaction of Gm peptide with membrane lipids and the formation of unilamellar giant vesicles (GUV), containing mixtures of neutral lipid-neutral palmitoyl oleoyl phosphatidylcholine (POPC) and negative lipid-loaded palmitoyl oleoyl phosphatidylglycerol (POPG) or cholesterol, thus imitating the behaviour of bacterial and mammalian cell membranes, respectively [ 94 ].…”

Section: Critical Issues Possible Solutions For Clinical Use Of Amentioning

confidence: 99%

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

et al. 2020

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Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells.

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Section: Critical Issues Possible Solutions For Clinical Use Of Amentioning

confidence: 99%

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

et al. 2020

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“…More recently, the spider-venom peptide Hi1a was shown to inhibit larval development of the barber's pole worm Haemonchus contortus, a parasite of sheep production [210]. Gomesin, a peptide found in the venom [211] and hemocytes [212] of spiders, has broad-spectrum activity against bacteria, fungi, parasites and tumor cells [213,214], and a cyclized version was recently shown to have improved stability and activity against Plasmodium in vitro [215].…”

Section: Antiparasitic Toxinsmentioning

confidence: 99%

Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery

Herzig

Cristofori-Armstrong

Israel

et al. 2020

Biochemical Pharmacology

129

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Venomous animals have evolved toxins that interfere with specific components of their victim's core physiological systems, thereby causing biological dysfunction that aids in prey capture, defense against predators, or other roles such as intraspecific competition. Many animal lineages evolved venom systems independently, highlighting the success of this strategy. Over the course of evolution, toxins with exceptional specificity and high potency for their intended molecular targets have prevailed, making venoms an invaluable and almost inexhaustible source of bioactive molecules, some of which have found use as pharmacological tools, human therapeutics, and bioinsecticides. Current biomedically-focused research on venoms is directed towards their use in delineating the physiological role of toxin molecular targets such as ion channels and receptors, studying or treating human diseases, targeting vectors of human diseases, and treating microbial and parasitic infections. We provide examples of each of these areas of venom research, highlighting the potential that venom molecules hold for basic research and drug development.

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“…[ 16 ] Gomesin affects programmed cell death through the expression levels of cell cycle proteins, by the generation of reactive oxygen species (ROS) and changes in the intracellular levels of Ca 2+ . [ 12 ] Regarding CLIP71, several mechanisms of action have been suggested, namely induction of apoptosis via upregulation of death effectors, by mitochondrial membrane permeabilization or changes in the mitochondrial membrane potential. [ 38 ]…”

Section: Figurementioning

confidence: 99%

Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles

Serna

Cano‐Garrido

Sánchez‐García

et al. 2020

Part & Part Syst Charact

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as self-assembling at the nanoscale, cell targeting and fluorescent emission, which might be useful for imaging purposes. This can be achieved by the construction of modular proteins that combine protein segments from different origins and with different biological activities. [3] Among such functions, the oligomerization within nanoscale dimensions and the multivalent display of cell surface peptidic ligands [4] are highly desirable to favor the enhanced retention and permeability (EPR) effect and a proper tumor biodistribution, and to estimulate the intracellular delivery in target tissues through cooperative cell binding. The incorporation of C-terminal polyhistidine peptides to modular proteins represents a simple strategy to promote robust self-assembling, as divalent metal and non-metal cations in the media, acting as molecular cross-linkers, induce protein clustering [5] and regular oligomerization in form of stable nanoparticles. [6,7] An N-terminal cationic region in the building blocks is also required for oligomerization. [6,7] Among cytotoxic proteins, venoms developed for animal predation and defense are particularly appealing as cytotoxic drugs, [8,9,10] and the possibility to engineer venoms as Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self-assembling multimeric nanoparticles. Incorporated in modular constructs including a C-terminal polyhistidine tag and an N-terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4 + tumor cells in a CXCR4-dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor-targeted nanomaterials for selective theragnostic applications in CXCR4 + cancers.

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The Biological and Biophysical Properties of the Spider Peptide Gomesin

Cited by 19 publications

References 55 publications

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities

Animal toxins — Nature’s evolutionary-refined toolkit for basic research and drug discovery

Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles

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