Université de Rennes 1, ICMV, UMR CNRS 6226, 263 Avenue du Général Leclerc, 35042 Rennes Cedex, France.
J Med Chem. 2012 Mar 8;55(5):2025-34. doi: 10.1021/jm2011595. Epub 2012 Feb 22.
Incorporation of aza-β(3)-amino acids into an endogenous neuropeptide from mollusks (ALSGDAFLRF-NH(2)) 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-β(3)-amino acids on peptide structure. The first three-dimensional structures of pseudopeptides containing aza-β(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.
将氮杂-β（3）-氨基酸掺入到具有弱抗菌活性的来自软体动物的内源性神经肽（ALSGDAFLRF-NH2）中，可以设计新的 AMP 序列。根据取代的性质，这可以使假肽失活，或者在没有高细胞毒性的情况下导致抗菌活性的急剧增强。通过 NMR 和圆二色性研究的假肽结构研究表明，氮杂-β（3）-氨基酸对肽结构的影响。含有氮杂-β（3）-氨基酸的假肽的第一个三维结构在含水胶束 SDS 中被确定，并证明在水溶液中可以形成酰肼环。因此，通过在肽序列中此类氨基酸类似物的性质和位置引起的结构修饰，可以调节 AMP 活性。
