Structure鈭扐ctivity Relationship, Conformational and Biological Studies of Temporin L Analogues

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• 作者：Maria Luisa Mangoni ; Alfonso Carotenuto ; Luigia Auriemma ; Maria Rosaria Saviello ; Pietro Campiglia ; Isabel Gomez-Monterrey ; Stefania Malfi ; Ludovica Marcellini ; Donatella Barra ; Ettore Novellino ; Paolo Grieco
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：March 10, 2011
• 年：2011
• 卷：54
• 期：5
• 页码：1298-1307
• 全文大小：872K
• 年卷期：v.54,no.5(March 10, 2011)
• ISSN：1520-4804

文摘

Temporins are naturally occurring peptides with promising features, which could lead to the development of new drugs. Temporin-1Tl (TL) is the strongest antimicrobial peptide, but it is toxic on human erythrocytes and this fact makes the design of synthetic analogues with a higher therapeutic index vital.We studied the structure鈭抋ctivity relationships of a library of TL derivatives focusing on the correlation between the 伪-helix content of the peptides, the nature of their cationic residues, and their antibacterial/antiyeast/hemolytic activities. We found that the percentage of helicity of TL analogues is directly correlated to their hemolytic activity but not to their antimicrobial activity. In addition, we found that the nature of positively charged residues can affect the biological properties of TL without changing the peptide鈥檚 helicity. It is noteworthy that a single amino acid substitution can prevent the antimicrobial activity of TL, making it a lytic peptide presumably due to its self-association. Last, we identified a novel analogue with properties that make it an attractive topic for future research.