Publicação
Analogues of the antimicrobial peptide BP214
| Resumo: | One of the most concerning health problems present in the twenty-first century is antibiotic-resistant infections. The growing number of multi-resistant infections has led to complicated public health problems that require the most consideration. Simultaneously there are economic and regulatory barriers. Having all of these difficulties in mind, some researchers are trying to find new therapeutic classes that may became reliable alternatives to the therapeutics use nowadays. One of these new classes may be antimicrobial peptides. AMPs have demonstrated antimicrobial activity which makes them a good choice for research. Their cationic amino acids confer the molecule an attraction towards some components of the bacteria, this leads to the possibility of destroying the microorganism due to membrane rupture. The AMP studied on this work was BP214, which was characterised in some previous studies. BP214 has shown a similar antimicrobial activity to colistin (a last-line therapeutic) and a reduced hemolytic activity compared to other AMPs. Therefore, on this study, eleven different BP214s analogues were synthesised and studied in order to discover which amino acids are essential to its antimicrobial and hemolytic activities. Each of these analogues differs from BP214 only in one amino acid that was replaced by an alanine. The results demonstrated that only the peptides that had a lysine or an arginine replaced showed an improved antimicrobial activity but also an increase in their hemolytic activity. The remaining replacements resulted in a loss of antimicrobial and hemolytic activities of the peptide. It was also possible to associate the loss of activity to the low hydrophobicity of the molecule, which resulted from the amino acids replacement. The peptides where the lysine or the arginine were replaced, were also the ones that demonstrated the higher hydrophobicity. Both amino acids are basic and possess high values of pKa. This characteristic can be closely related with higher antimicrobial activity. |
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| Autores principais: | Freire, Catarina Maria Boto |
| Assunto: | Gram-negative infections Antimicrobial peptides Antimicrobial activity Hemolytic activity Hydrophobicity Mestrado Integrado - 2017 |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | One of the most concerning health problems present in the twenty-first century is antibiotic-resistant infections. The growing number of multi-resistant infections has led to complicated public health problems that require the most consideration. Simultaneously there are economic and regulatory barriers. Having all of these difficulties in mind, some researchers are trying to find new therapeutic classes that may became reliable alternatives to the therapeutics use nowadays. One of these new classes may be antimicrobial peptides. AMPs have demonstrated antimicrobial activity which makes them a good choice for research. Their cationic amino acids confer the molecule an attraction towards some components of the bacteria, this leads to the possibility of destroying the microorganism due to membrane rupture. The AMP studied on this work was BP214, which was characterised in some previous studies. BP214 has shown a similar antimicrobial activity to colistin (a last-line therapeutic) and a reduced hemolytic activity compared to other AMPs. Therefore, on this study, eleven different BP214s analogues were synthesised and studied in order to discover which amino acids are essential to its antimicrobial and hemolytic activities. Each of these analogues differs from BP214 only in one amino acid that was replaced by an alanine. The results demonstrated that only the peptides that had a lysine or an arginine replaced showed an improved antimicrobial activity but also an increase in their hemolytic activity. The remaining replacements resulted in a loss of antimicrobial and hemolytic activities of the peptide. It was also possible to associate the loss of activity to the low hydrophobicity of the molecule, which resulted from the amino acids replacement. The peptides where the lysine or the arginine were replaced, were also the ones that demonstrated the higher hydrophobicity. Both amino acids are basic and possess high values of pKa. This characteristic can be closely related with higher antimicrobial activity. |
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