Cell-Penetrating Peptides Derived from Animal Venoms and Toxins.

Gandhi Rádis-Baptista

doi:10.3390/toxins13020147

Abstract

Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria) and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic properties, along with membrane permeation, translocation and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology. In this review, I aimed to collate examples of peptides from animal venoms and toxic secretions that possess the ability to penetrate diverse types of cells. These venom CPPs have been chemically or structurally modified to enhance cell selectivity, bioavailability and a range of target applications. Herein, examples are listed and discussed, including cysteine-stabilized and linear, α-helical peptides, with cationic and amphipathic character, from the venom of insects (e.g., melittin, anoplin, mastoparans), arachnids (latarcin, lycosin, chlorotoxin, maurocalcine/imperatoxin homologs and wasabi receptor toxin), fish (pardaxins), amphibian (bombesin) and snakes (crotamine and cathelicidins).

Highlights

IntroductionIt has been established that the more diverse a biome is, the more intricate is the chemical-ecological relationships among organisms sharing the same niche and richer is the diversity of molecules and pharmacological activities that these co-inhabiting organisms contain
The holistic molecular genetic analyses of venomous animals utilizing, for example, transcriptome in combination with proteome studies of venom glands, have revealed the diversity of a set of substances produced by a given organism that inhabits a particular biome and the uniqueness of such molecular repertoire expressed as active components of biological materials, such as venoms [4,5,6,7,8]
Animal venoms are a blend of bioactive peptides, among other organic and enzymatic components, that in combination and synergistically disrupt the physiological processes of prey and/or victims

Summary

Introduction

It has been established that the more diverse a biome is, the more intricate is the chemical-ecological relationships among organisms sharing the same niche and richer is the diversity of molecules and pharmacological activities that these co-inhabiting organisms contain. Animal venoms and skin secretions are rich biological materials that contain a blend of biologically and pharmacologically active components, used by venomous and poisonous organisms for defense, predation and territorial disputes. The holistic molecular genetic analyses of venomous animals utilizing, for example, transcriptome in combination with proteome studies of venom glands, have revealed the diversity of a set of substances produced by a given organism that inhabits a particular biome and the uniqueness of such molecular repertoire expressed as active components of biological materials, such as venoms [4,5,6,7,8]

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Discussion

Conclusion