Kerkis Irina, de Brandão Prieto da Silva Alvaro Rossan, Pompeia Celine, Tytgat Jan, de Sá Junior Paulo L
Laboratório de Genética, Instituto Butantan, Av. Vital Brasil 1500, São Paulo, SP, 05503-900, Brazil.
Toxicology and Pharmacology, University of Leuven (KU Leuven), Louvain, Belgium.
Cell Mol Life Sci. 2017 Feb;74(4):647-661. doi: 10.1007/s00018-016-2343-6. Epub 2016 Aug 23.
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.
毒素已被证明具有多种生物学功能，并且是药物和生物技术工具的丰富来源。我们关注的毒素不仅具有特定活性，还含有负责跨膜渗透的残基，这些残基可被视为生物肽——一类具有内在生物活性的细胞穿透肽。生物肽是药理学和生物技术中的潜在工具，因为它们有助于将物质和纳米颗粒递送至细胞内靶点。迄今为止鉴定出的生物肽是源自人类蛋白质的肽，如细胞色素c（CYCS）、降钙素受体（卡姆肽）和内皮型一氧化氮合酶（诺桑吉肽）。然而，毒素通常不被视为潜在的生物肽。在本综述中，我们基于结构活性关系、最小化和生物活性研究，讨论将一些毒素及其衍生分子纳入一类新的生物肽。对毒素衍生生物肽及其短分子变体的氨基酸残基组成进行比较分析，是一种创新的分析策略，使我们能够了解天然毒素在体内的多功能性，并规划新型药理学和生物技术产品。此外，我们还讨论了许多生物肽毒素如何具有对细胞穿透和生物活性都很重要的刚性两亲结构。
