RESUMO
Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of many organisms and are promising candidates to treat infections caused by pathogenic bacteria to animals and humans. AMPs also display anticancer activities because of their ability to inactivate a wide range of cancer cells. Cancer remains a cause of high morbidity and mortality worldwide. Therefore, the development of methods for its control is desirable. Attractive alternatives include plant AMP thionins, defensins, and cyclotides, which have anticancer activities. Here, we provide an overview of plant AMPs anticancer activities, with an emphasis on their mode of action, their selectivity, and their efficacy.
Assuntos
Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antineoplásicos/uso terapêutico , Imunidade Inata/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Animais , Anti-Infecciosos/uso terapêutico , Ciclotídeos/uso terapêutico , Defensinas/uso terapêutico , Humanos , Imunidade Inata/imunologia , Neoplasias/patologia , Plantas/química , Tioninas/uso terapêuticoRESUMO
Plant defensins are cationic peptides that are ubiquitous within the plant kingdom and belong to a large superfamily of antimicrobial peptides found in several organisms collectively called defensins. The primary structure of these peptides includes 45 to 54 amino acid residues with considerable sequence variation. At the level of three-dimensional structure, they are small and globular, composed of three anti-parallel ß-sheets and one α-helix, which is highly conserved among these peptides. The three-dimensional structure is stabilized by four disulfide bridges formed by eight strictly conserved Cys residues. Two of these bridges compose the Cys-stabilized α-helix ß-strand motif, which is found in other peptides with biological activities. Plant defensins present numerous biological activities, such as inhibiting protein synthesis, ion channel function and α-amylase and trypsin activity; impairing microbial, root hair and parasitic plant growth; mediating abiotic stress and Zn tolerance; altering ascorbic acid redox state; stimulating sweet taste sensation; serving as epigenetic factors; affecting self-incompatibility; and promoting male reproductive development. Some of these biological activities, such as microbial growth inhibition and sweet taste induction, coupled with a scaffold that provides these peptides with incredible physicochemical resistance to harsh environments and the potential for simple amino acid substitution, raise the opportunity to improve the function of defensins or introduce new activities, endowing these peptides with great biotechnological and medical significance. This review will cover the biological activities and roles of plant defensins and will focus on their application in the field of biotechnology.
Assuntos
Biotecnologia , Defensinas , Descoberta de Drogas/métodos , Plantas , Sequência de Aminoácidos , Animais , Defensinas/genética , Defensinas/isolamento & purificação , Defensinas/farmacologia , Defensinas/uso terapêutico , Humanos , Dados de Sequência Molecular , Fenômenos Fisiológicos Vegetais , Estruturas Vegetais/química , Plantas/química , Plantas Geneticamente Modificadas/química , Conformação Proteica , Alinhamento de Sequência , Especificidade da EspécieRESUMO
We show that RsAFP2, a plant defensin that interacts with fungal glucosylceramides, is active against Candida albicans, inhibits to a lesser extent other Candida species, and is nontoxic to mammalian cells. Moreover, glucosylceramide levels in Candida species correlate with RsAFP2 sensitivity. We found RsAFP2 prophylactically effective against murine candidiasis.
Assuntos
Antifúngicos , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Defensinas , Proteínas de Plantas , Animais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida/classificação , Candida/isolamento & purificação , Candida albicans/efeitos dos fármacos , Candida albicans/isolamento & purificação , Candidíase/microbiologia , Defensinas/metabolismo , Defensinas/farmacologia , Defensinas/uso terapêutico , Glucosilceramidas/metabolismo , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Proteínas de Plantas/metabolismo , Proteínas de Plantas/farmacologia , Proteínas de Plantas/uso terapêutico , Resultado do TratamentoRESUMO
Worldwide, tuberculosis remains the most important infectious disease causing morbidity and death. Currently, at least one-third of the world's population is infected with Mycobacterium tuberculosis. In addition, the World Health Organization estimates that about 8-10 million new tuberculosis cases occur annually worldwide and this incidence is currently increasing. Moreover, multidrug-resistant tuberculosis has been increasing in incidence in many areas during the past decade. These situations underscore the importance of the development of new therapeutic agents against mycobacterial infectious diseases. In this article, it is review current progress in the understanding of antimicrobial peptides as potential candidates to develop an alternative/adjunct therapeutic strategy against tuberculosis. This immunoadjunctive therapy might be evaluated in the context of possible drug resistance. This review also summarizes the knowledge about the functions of antimicrobial peptides in the pulmonary innate host defense system and their role in mycobacterial infection, and at the same time outlines recent advances in our understanding of the combined effect of antimicrobial peptides and anti-tuberculosis drugs against intracellular mycobacteria. A concerted effort should now focus on the clinical application of antimicrobial peptides for their practical use.
Assuntos
Anti-Infecciosos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Infecções por Mycobacterium/tratamento farmacológico , Tuberculose/tratamento farmacológico , Animais , Anti-Infecciosos/metabolismo , Peptídeos Catiônicos Antimicrobianos/metabolismo , Defensinas/metabolismo , Defensinas/uso terapêutico , HumanosRESUMO
Human defensins are endogenous antimicrobial peptides with prophylactic and therapeutic potential against HIV. The ability of defensins to bind the HIV envelope could be exploited to design topic agents that block viral entry into exposed mucosa. Additionally, their capacity to inhibit viral replication, complement system activation, dendritic and memory T cells chemoattraction, together with peptide engineering could bring about new and better antiretroviral drugs. Clinical trials could be demonstrated the efficacy of defensins against HIV in clinical practice.
Assuntos
Anti-Infecciosos/uso terapêutico , Defensinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ensaios Clínicos como Assunto , Infecções por HIV/prevenção & controle , HumanosRESUMO
Las defensinas humanas son péptidos antimicrobianos de síntesis endógena, con potencial profiláctico y terapéutico anti VIH. La aplicación de las defensinas como agentes tópicos en mucosas expuestas podría bloquear la entrada del VIH, debido a la capacidad de estos péptidos de unirse a la envoltura viral. Además, la capacidad de las defensinas para inhibir la replicación del virus, activar el sistema del complemento y quimiotaxis hacia células dendríticas y células T de memoria, permitirá diseñar mejores drogas antiretrovirales, siendo necesario evaluar la eficacia de las defensinas en la práctica clínica.
Human defensins are endogenous antimicrobial peptides with prophylactic and therapeutic potential against HIV. The ability of defensins to bind the HIV envelope could be exploited to design topic agents that block viral entry into exposed mucosa. Additionally, their capacity to inhibit viral replication, complement system activation, dendritic and memory T cells chemoattraction, together with peptide engineering could bring about new and better antiretroviral drugs. Clinical trials could be demonstrated the efficacy of defensins against HIV in clinical practice.