Membrane-translocating peptides and toxins: from nature to bedside

Abstract

Atualmente, diferentes classes funcionais de peptídeos e toxinas biologicamente ativas isolados de diversos organismos são conhecidas. Em medicina, esses polipeptídios podem ser diretamente utilizados ou podem servir como modelos para a geração de moléculas derivadas. Aqui, nós fazemos referência a três classes de peptídeos e toxinas que agem sobre membranas celulares ou sobre sistemas de transporte por membranas: (i) toxinas binárias; (ii) peptídeos antimicrobianos; (iii) peptídeos penetradores de células. As toxinas binárias têm sido geneticamente manipuladas para gerar imunotoxinas específicas, enquanto os peptídeos antimicrobianos são usados como agentes alternativos contra células tumorais e microbianas resistentes. Os peptídeos penetradores de células têm aplicações que vão desde a transfecção celular quanto ao transporte intracelular de nanopartículas. Nosso grupo vem investigando a capacidade da crotamina, um peptídeo do veneno de cascavel, em translocar membranas celulares, bem como de utilizar a crotamina como sistema de transporte molecular e de análise de imagens.Today, different functional classes of bioactive peptides and toxins isolated from diverse sources of living organisms are known. In medicine, these polypeptides present the potential to be used structurally unmodified or to serve as templates for molecular design of improved derivatives. Here, we refer to members of three classes of remarkable peptides and toxins that act at the cell membranes level and membrane trafficking systems: (i) the binary toxins (ii) the antimicrobial peptides and (iii) the cell penetrating peptides. Binary toxins have been genetically manipulated to generate specific immunotoxins, while antimicrobial peptides are in use as alternative agents against resistant microbes and tumor cells. Cell penetrating peptides have applications as diverse as cell transfection and transport of nanomaterials. Our group is dissecting the capacity of crotamine, a peptide from rattlesnake venom, to translocate cell membranes and use it as a delivery system in the transducing technology and molecular imaging.Keywords: cytolysin, binary toxin, antimicrobial peptide, cell-penetrating peptide, animal toxin, nanobiotechnology Binary Bacterial ToxinsA wide variety of bacterial toxins that has the cell membrane as a target is presently known. Indeed the molecular diversity of bacterial toxins is so remarkable that a large number of microorganisms secret several toxic peptides and polypeptides devoid of or having catalytic activity. All these toxins are capable of intoxicating eucaryotic cells by interfering directly with cytoplasmic membrane or by using membrane systems to gain access Membrane-translocating Peptides and Toxins: from Nature to Bedside J. Braz. Chem. Soc. 212 to the interior of cells for the delivery of their active domain.In the first case, single chain proteins or composed of two separate water-soluble proteins -which oligomerize during their action on phospholipid membrane and form pores or channels -encompass the cytoly...

Preparation and Characterization of Gelonin-Melittin Fusion Biotoxin for Synergistically Enhanced Anti-Tumor Activity

“…Biotoxins are a group of proteins and peptides produced from various biological origins that play important roles in the host defense system for survival against predators (1, 2). Despite varied underlying mechanisms, these biotoxins are commonly cytotoxic and thus have been considered as attractive anti-cancer drug candidates (3, 4).…”

CyLoP-1: A Novel Cysteine-Rich Cell-Penetrating Peptide for Cytosolic Delivery of Cargoes

“…24 Crotamine has been shown to be a potential CPP with targeting ability. [25][26][27] It is a 42 amino acid long polypeptide containing two putative nuclear localization sequence (NLS) motifs, namely, Crot (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and Crot (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). 27 We selected the C-terminal NLS Crot (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) as starting sequence for structure-activity relationship (SAR) studies.…”

The effect of Ricinus communis seeds extract on reproductive activity and blood values of male rabbits

“…The reduced content of head of epididymis from sperms in males expose to plant extracts can attributed to reduced level of testosterone hormone, as (27,28) referred to presence of receptors for testosterone in sperms in their early stages and the primary sperm cells and they strongly referred to the importance of this hormone in all stages of sperm genesis only in stage of spermatogenesis. Also they referred to possibility of continuity of spermatogenesis in make from which their pituitary gland removed by androgens injection.The significant reduction in the sperm count can be attributed to the direct effect of ricin on the spermatozoa, since the spermatozoa has sugar residues like galactose, acetylgalactosamine, and Dmannose known by the Glycoconjugates or glycocalyx (29), these residues form a target to the ricin toxin B chain (RTB) which considered the binding domain of ricin to the surface of the eukaryotic cells (30). There sequences of interactive binding presumably prevent protein synthesis which led to cellular death (31).…”