Laboratorio de Química Farmacéutica, Departamento de Química Orgánica, Facultad de Química, Universidad de la República, General Flores 2124, Montevideo 11800, Uruguay.
Estación Experimental Dr. Mario A. Cassinoni, Facultad de Agronomía, Universidad de la República, Ruta 3 Km 363, Paysandú 60000, Uruguay.
Molecules. 2022 Oct 29;27(21):7350. doi: 10.3390/molecules27217350.
The synthesis of cyclotetrapeptides analogues of the natural products tentoxin and versicotide D was achieved in good yield by solid phase peptide synthesis (SPPS) of their linear precursors and solution phase cyclization. All the cyclopeptides and several open precursors were evaluated as herbicides. Five cyclopeptides and five lineal peptides showed a significant inhibition (>70%) of Ryegrass seed’s radicle growth at 67 μg/mL. The evaluation at lower concentrations (4−11 μM) indicates two cyclopeptides analogs of tentoxin, which present one (N-Methyl-d-Phe), and two N-MeAA (N-Methyl-Ala and N-Methyl-Phe), respectively, as the most active of them, showing remarkable phytotoxic activity. In two cases, the open precursors are as active as their corresponding cyclopeptide. However, many linear peptides are inactive and their cyclization derivatives showed herbicidal activity. In addition, two cyclopeptide analogues of versicotide D showed more improved activity than the natural product. The results indicate that the peptide sequence, the amino acid stereochemistry and the presence of N-methyl group have important influence on the phytotoxic activity. Moreover, several compounds could be considered as lead candidates in the development of bioherbicides.
通过固相肽合成（SPPS）线性前体和溶液相环化，以高产率合成了天然产物 tentoxin 和 versicotide D 的环四肽类似物。所有环肽和几个开环前体都被评估为除草剂。五种环肽和五种线性肽在 67 μg/mL 时对黑麦草种子胚根生长表现出显著抑制（>70%）。在较低浓度（4-11 μM）下的评估表明，两种 tentoxin 的环肽类似物，分别具有一个（N-甲基-d-Phe）和两个 N-MeAA（N-甲基-Ala 和 N-甲基-Phe），是最活跃的，表现出显著的植物毒性活性。在两种情况下，开环前体与相应的环肽一样具有活性。然而，许多线性肽没有活性，它们的环化衍生物表现出除草活性。此外，两种 versicotide D 的环肽类似物显示出比天然产物更高的活性。结果表明，肽序列、氨基酸立体化学和 N-甲基的存在对植物毒性活性有重要影响。此外，一些化合物可以被认为是生物除草剂开发的先导候选物。
