title: Toxin bioportides: exploring toxin biological activity and multifunctionality.
abstract: Toxins have been shown to have many biological functions and to constitute a rich source of drugs and biotechnological tools. We focus on toxins that not only have a specific activity, but also contain residues responsible for transmembrane penetration, which can be considered bioportides-a class of cell-penetrating peptides that are also intrinsically bioactive. Bioportides are potential tools in pharmacology and biotechnology as they help deliver substances and nanoparticles to intracellular targets. Bioportides characterized so far are peptides derived from human proteins, such as cytochrome c (CYCS), calcitonin receptor (camptide), and endothelial nitric oxide synthase (nosangiotide). However, toxins are usually disregarded as potential bioportides. In this review, we discuss the inclusion of some toxins and molecules derived thereof as a new class of bioportides based on structure activity relationship, minimization, and biological activity studies. The comparative analysis of the amino acid residue composition of toxin-derived bioportides and their short molecular variants is an innovative analytical strategy which allows us to understand natural toxin multifunctionality in vivo and plan novel pharmacological and biotechnological products. Furthermore, we discuss how many bioportide toxins have a rigid structure with amphiphilic properties important for both cell penetration and bioactivity.
authors.affiliation: Laboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil. irina.kerkis@butantan.gov.br.
authors.forename: Irina
authors.initials: I
authors.lastname: Kerkis
authors.affiliation: Laboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
authors.forename: Alvaro Rossan
authors.initials: AR
authors.lastname: de Brandão Prieto da Silva
authors.affiliation: Laboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
authors.forename: Celine
authors.initials: C
authors.lastname: Pompeia
authors.affiliation: Toxicology and Pharmacology, University of Leuven (KU Leuven), Louvain, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.affiliation: Laboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil. paulsaj2001@yahoo.com.br.
authors.forename: Paulo L
authors.initials: PL
authors.lastname: de Sá Junior
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism*; D003435:Crotalid Venoms / Q000737:chemistry / Q000378:metabolism; D017839:Crotalus / Q000378:metabolism; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008958:Models, Molecular; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism; D012605:Scorpions / Q000378:metabolism; D014118:Toxins, Biological / Q000737:chemistry* / Q000378:metabolism*; D014757:Viper Venoms / Q000737:chemistry / Q000378:metabolism; D017819:Viperidae / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D003435:Crotalid Venoms; D012604:Scorpion Venoms; D014118:Toxins, Biological; D014757:Viper Venoms; C105361:imperatoxin A; C406406:maurocalcine; C091539:Chlorotoxin; C018932:myotoxin A; D045304:Cytochromes c; C010563:crotamine
keywords: Bioportide; Cargo delivery; Cell-penetrating peptides; Chlorotoxin; Crotamine; Toxins