LIPPSO, Department of Chemistry, Campus Montilivi, University of Girona, 17004 Girona, Spain.
Laboratory of Plant Pathology, Institute of Food and Agricultural Technology-CIDSAV-XaRTA, Campus Montilivi, University of Girona, 17004 Girona, Spain.
Int J Mol Sci. 2021 Jun 21;22(12):6631. doi: 10.3390/ijms22126631.
From a previous collection of lipopeptides derived from , we selected 18 sequences in order to improve their biological profile. In particular, analogues containing a D-amino acid at position 4 were designed, prepared, and tested against plant pathogenic bacteria and fungi. The biological activity of these sequences was compared with that of the corresponding parent lipopeptides with all L-amino acids. In addition, the influence of the length of the hydrophobic chain on the biological activity was evaluated. Interestingly, the incorporation of a D-amino acid into lipopeptides bearing a butanoyl or a hexanoyl chain led to less hemolytic sequences and, in general, that were as active or more active than the corresponding all L-lipopeptides. The best lipopeptides were and , both incorporating a D-Phe at position 4 and a butanoyl group, with MIC values between 0.8 and 6.2 µM, low hemolysis (0 and 24% at 250 µM, respectively), and low phytotoxicity. Characterization by NMR of the secondary structure of revealed that the D-Phe at position 4 disrupts the α-helix and that residues 6 to 10 are able to fold in an α-helix. This secondary structure would be responsible for the high antimicrobial activity and low hemolysis of this lipopeptide.
从先前从 中分离得到的脂肽中，我们选择了 18 个序列，以改善它们的生物学特性。特别是，设计、制备并测试了含有 4 位 D-氨基酸的类似物，以对抗植物病原细菌和真菌。这些序列的生物活性与所有 L-氨基酸的相应母体脂肽进行了比较。此外，还评估了疏水性链的长度对生物活性的影响。有趣的是，将 D-氨基酸掺入带有丁酰基或己酰基链的脂肽中会导致溶血活性较低的序列，并且通常比相应的全 L-脂肽具有相同或更高的活性。最好的脂肽是 和 ，它们都在 4 位含有 D-Phe 和丁酰基，MIC 值在 0.8 到 6.2 μM 之间，溶血率低（分别为 0 和 24%，在 250 μM 时），且低植物毒性。通过 NMR 对 的二级结构进行表征表明，4 位的 D-Phe 破坏了 α-螺旋，并且 6 到 10 位残基能够折叠成 α-螺旋。这种二级结构可能是该脂肽具有高抗菌活性和低溶血率的原因。
