From a Marine Neuropeptide to Antimicrobial Pseudopeptides Containing Aza-尾3-Amino Acids: Structure and Activity

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• 作者：Mathieu Laurencin ; Baptiste Legrand ; Emilie Duval ; Jo毛l Henry ; Mich猫le Baudy-Floc鈥檋 ; C茅line Zatylny-Gaudin ; Arnaud Bondon
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：March 8, 2012
• 年：2012
• 卷：55
• 期：5
• 页码：2025-2034
• 全文大小：515K
• 年卷期：v.55,no.5(March 8, 2012)
• ISSN：1520-4804

文摘

Incorporation of aza-尾³-amino acids into an endogenous neuropeptide from mollusks (ALSGDAFLRF-NH₂) with weak antimicrobial activity allows the design of new AMPs sequences. Depending on the nature of the substitution, this can render the pseudopeptides inactive or lead to a drastic enhancement of the antimicrobial activity without high cytotoxicity. Structural studies of the pseudopeptides carried out by NMR and circular dichroism show the impact of aza-尾³-amino acids on peptide structure. The first three-dimensional structures of pseudopeptides containing aza-尾³-amino acids in aqueous micellar SDS were determined and demonstrate that the hydrazino turn can be formed in aqueous solution. Thus, AMP activity can be modulated through structural modifications induced by the nature and the position of such amino acid analogues in the peptide sequences.