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Publication
Péptidos antimicrobianos : estrutura, classificação e mecanismo de acção
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Advisor(s)
Abstract(s)
Apesar de terem sido descobertos há quase um século, os péptidos antimicrobianos não tiveram uma grande relevância no panorama farmacêutico devido ao aparecimento dos antibióticos. Com o surgimento de uma variedade imensa de resistências a estes meios de combate aos agentes patogénicos, são necessárias novas terapêuticas alternativas às terapêuticas de primeira linha. Daí que o estudo destes péptidos tenha sido reforçado nos últimos anos.
Os péptidos antimicrobianos são péptidos geralmente curtos e anfipáticos que podem ser encontrados no sistema imunitário inato dos mais variados organismos. Estes
possuem um espectro de atividade diversificado, visto serem ativos contra variados
tipos de microrganismos (desde bactérias a parasitas). A sua propensão para a formação de estruturas secundárias regulares, quando em contacto com as membranas biológicas, permite que estes péptidos sejam classificados de acordo com esse nível de estrutura.
No entanto, e mais importante, as propensões dos péptidos antimicrobianos para formar
estruturas secundárias conferem diferenças quer nos seus mecanismos de ação, quer nos seus alvos. Assim, quando a ação é exercida sobre a membrana celular, geralmente
ocorre por mecanismos de rutura e permeabilização. Quando a ação é sobre funções
celulares, os péptidos atuam por interação com proteínas.
Embora alguns microrganismos possuam ou consigam adquirir resistências contra este tipo de péptidos, tais resistências são difíceis de obter devido à grande diversidade e especificidade destes.
No futuro, prevê-se que o estudo destes péptidos antimicrobianos continue a aumentar e que a quantidade de péptidos em ensaios clínicos também incremente. Os seus benefícios terapêuticos, em conjunto com a sua boa tolerabilidade e seletividade,
antecipam uma alternativa terapêutica aos fármacos atuais, no combate aos microrganismos altamente resistentes.
Although they were discovered almost a century ago, antimicrobial peptides did not have a great relevance in the pharmaceutical scene due to the appearance of antibiotics. With the emergence of an immense variety of resistance to these pathogen-fighting agents, new therapeutic alternatives to first-line therapies are necessary. Hence the study of these peptides has been strengthened in recent years. The antimicrobial peptides are generally short and amphipathic peptides that can be found in the innate immune system of the most varied organisms. These peptides have a diversified spectrum of activity, since they are active against several types of microorganisms (from bacteria to parasites). Their propensity for the formation of regular secondary structures, when in contact with biological membranes, allows these peptides to be classified according to this level of structure. However, and more importantly, the propensities of antimicrobial peptides to form secondary structures confer differences in both their mechanisms of action and their targets. Thus, when the action is exerted on the cell membrane, it usually occurs by mechanisms of rupture and permeabilization. When the action is on cellular functions, the peptides act by interaction with proteins. Although some microorganisms possess or are able to acquire resistance against this type of peptides, such resistances are difficult to obtain because of their great diversity and specificity. In the future, it is anticipated that the study of these antimicrobial peptides will continue to increase and that the amount of peptides in clinical trials will also increase. Their therapeutic benefits, together with their good tolerability and selectivity, anticipate a therapeutic alternative to current drugs in the fight against highly resistant microorganisms.
Although they were discovered almost a century ago, antimicrobial peptides did not have a great relevance in the pharmaceutical scene due to the appearance of antibiotics. With the emergence of an immense variety of resistance to these pathogen-fighting agents, new therapeutic alternatives to first-line therapies are necessary. Hence the study of these peptides has been strengthened in recent years. The antimicrobial peptides are generally short and amphipathic peptides that can be found in the innate immune system of the most varied organisms. These peptides have a diversified spectrum of activity, since they are active against several types of microorganisms (from bacteria to parasites). Their propensity for the formation of regular secondary structures, when in contact with biological membranes, allows these peptides to be classified according to this level of structure. However, and more importantly, the propensities of antimicrobial peptides to form secondary structures confer differences in both their mechanisms of action and their targets. Thus, when the action is exerted on the cell membrane, it usually occurs by mechanisms of rupture and permeabilization. When the action is on cellular functions, the peptides act by interaction with proteins. Although some microorganisms possess or are able to acquire resistance against this type of peptides, such resistances are difficult to obtain because of their great diversity and specificity. In the future, it is anticipated that the study of these antimicrobial peptides will continue to increase and that the amount of peptides in clinical trials will also increase. Their therapeutic benefits, together with their good tolerability and selectivity, anticipate a therapeutic alternative to current drugs in the fight against highly resistant microorganisms.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
Keywords
Péptido antimicrobiano Microrganismo Fármaco Sistema imunitário