Hemocidinas derivadas da hemoglobina: estruturas, propriedades e perspectivas

Abstract

Recebido em 13/12/12; aceito em 23/4/13; publicado na web em 10/6/13 HEMOCIDINS DERIVED FROM HEMOGLOBIN: STRUCTURES, PROPERTIES AND PERSPECTIVES. The increasing incidence of microbial infections, high toxicity, and high level of resistance associated with conventional antibiotics has created a need for new drugs. Antimicrobial peptides (AMPs) constitute a promising alternative and/or an important source of knowledge given their ability to inhibit the growth and/or to kill bacteria, fungi, parasites and/or viruses through mechanisms of action different from those of non-peptide drugs. This review focused on this important class of organic compounds that includes hemocidins resulting from hemoglobin proteolysis in vivo and in vitro or from chemical synthesis, subject of research in foreign and Brazilian laboratories.Keywords: hemoglobin; antimicrobial peptides; microbial resistance. PEPTÍDEOS ANTIMICROBIANOS (AMPs)Há décadas, o fato de sermos constantemente bombardeados por inúmeras espécies de microrganismos capazes de nos causar doenças chamou a atenção da comunidade científica, a qual acabou por evidenciar em nosso corpo um sistema imune inato adaptativo capaz de enfrentar esse problema. Faz parte desta imunidade inata os peptídeos antimicrobianos (geralmente denominados AMPs), que são rapidamente mobilizados para neutralizar um amplo espectro de micróbios. 1,2O primeiro relato da existência dos AMPs se deu em 1980 com o isolamento das cecropinas a partir da hemolinfa de mariposa Hyalophora cecropia.3 Um ano depois, as a-defensinas também foram isoladas e caracterizadas de leucócitos de mamíferos. 4 Nos humanos, os AMPs inatos mais proeminentes são as catelicidinas e defensinas (produzidas pelas células do sistema imune), bem como as histatinas (produzidas e secretadas na saliva pelas glândulas salivares). 1Segundo Cederlund e colaboradores, até 2011, mais de 1700 AMPs haviam sido identificados em fontes naturais variadas ou previstos através das sequências de genes que os codificam.5 Embora este número seja alto e eles exibam vasta diversidade de sequências de aminoácidos, algumas características químicas e estruturais são compartilhadas. Características gerais dos AMPsDe fato, a maioria dos AMPs que atuam sobre a membrana celular é formada por 12-50 resíduos de aminoácidos unidos entre si por ligações amida (denominadas peptídicas), apresenta carga líquida positiva (+2 a +9) em pH fisiológico e estrutura anfipática 6 com aproximadamente 50% de resíduos de aminoácidos hidrofóbicos.7 Estas características parecem ser fundamentais para a atividade contra a célula microbiana, já que a etapa inicial de seus mecanismos de ação é a sua atração eletrostática pelos grupos carregados negativamente de compostos da parede e da membrana celular. A hidrofobicidade dos AMPs auxilia posteriormente na sua inserção e forte interação com a bicamada lipídica. 5Muitos AMPs são amidados em sua carboxila terminal e/ou contém pontes dissulfeto envolvendo resíduos de cisteína e/ou piroglutamato como resíduo de aminoácido N-terminal e...

Antimicrobial activity of apitoxin, melittin and phospholipase A2 of honey bee (Apis mellifera) venom against oral pathogens

“…According to Carvalho and Machini (2013), AMPs have some advantageous properties: easy metabolism, low microbial resistance, microbicidal action, synergistic effects with other antibiotic drugs, and broad action spectrum. Hence, investigations into AMPs shall increase the current knowledge about drugs and aid in design of novel pharmaceuticals.…”

“…Melittin is cytotoxic and has potential action in cell lysis, as evidenced for human erythrocyte lysis (Pandey et al 2010) as well as other peptides. Furthermore, it acts directly on the cell membrane (Zhu et al 2007, Carvalho andMachini 2013). Several biological activities have been attributed to melittin, including antibacterial, antiviral, and anti-inflammatory actions, cell growth inhibition, and apoptosis of different cancer cell lines (Raghuraman and Chattopadhyay 2007, Wang et al 2009, Alia et al 2013.…”

Evidences for the action mechanism of angiotensin II and its analogs onPlasmodiumsporozoite membranes

“…Permeabilization in vivo may be associated with time and length scales that are orders‐of‐magnitude longer than considered in simulations. It has been suggested, for instance, that antimicrobial peptides may organize into bigger assemblies that are responsible for membrane permeabilization . Despite these limitations, our simulations revealed subtle differences in the behavior of the peptides.…”

Jelleine, a Family of Peptides Isolated from the Royal Jelly of the Honey Bees (Apis mellifera), as a Promising Prototype for New Medicines: A Narrative Review

“…Currently, five different membrane-target models are considered to explain the mode of action of AMPs on biological membranes [64,65]: (i) the Barrel-stave model, in which the peptide monomers associate and form a bundle of helices embedded in the membrane, forming a transmembrane channel [66]; (ii) the toroidal pore model (also called wormhole), in which the amphipathic peptide interacts electrostatically with the phospholipid-plasma membrane in a perpendicular orientation relative to the membrane bilayer. In this way, the peptide exerts pressure on the membrane and separates the polar heads elements of phospholipids, resulting in the upper lipid monolayer curving bend through the pore in such a way that the pore lumen consists of peptide molecules and polar heads of phospholipids mixed together [66]; (iii) the carpet-like model, in which the AMP accumulates on the surface of the plasmatic membrane due to the electrostatic interaction between the positively charged peptide residues and the negative charges of phospholipids, covering it similarly to a carpet, which lead to membrane permeabilisation [65,66]; (iv) the aggregate channel model, which assumes that a supramolecular peptide-lipid complex is formed that mediates the mutually coupled trans-bilayer transport of lipid and peptides, implicitly assuming that informal aqueous channels exist within these aggregates, allowing the free passage of ions and possibly larger molecules [64,67]; and (v) the detergent-like model, in which AMPs aggregates in the membrane surface and after reach a critical concentration promote a micellisation process in the phospholipid bilayer [65]. Molecular dynamics simulations showed that jelleine-I acts by increasing the pressure on the lipid bilayer of the bacterial membrane [50].…”