Tripropeptin C, a non-ribosomal cyclic lipopeptide containing three proline residues, exhibits excellent efficacy in the mouse-methicillin-resistant Staphylococcus aureus septicemia model. Since tripropeptins contain L-prolyl-D-proline and, as a result, are known to form a hairpin structure in proteins, it was of interest to determine whether this substructure contributes to their antibacterial activity. In this study, prolines in tripropeptin C were replaced with pipecolic acid(s) using precursor-directed biosynthesis. Only a new tripropeptin analog, tripropeptin Cpip, which has one L-pipecolic acid in place of L-proline, was isolated. The in vitro antimicrobial activity of the new analog was approximately two to four times weaker activity against Gram-positive bacteria, including drug-resistant species, compared with that of tripropeptin C. These results suggest that the L-prolyl-D-proline substructure plays an important role in the observed potency of tripropeptins.

Tripropeptin C 是一种含有三个脯氨酸残基的非核糖体环状脂肽，在小鼠耐甲氧西林金黄色葡萄球菌败血症模型中表现出优异的功效。由于三肽肽含有L-脯氨酰-D-脯氨酸，因此已知其在蛋白质中形成发夹结构，因此有兴趣确定该子结构是否有助于其抗菌活性。在本研究中，利用前体定向生物合成，用哌可酸取代三丙肽 C 中的脯氨酸。仅分离出一种新的三丙肽类似物三丙肽Cpip，其用一个L-哌啶酸代替L-脯氨酸。与三肽肽 C 相比，新类似物对革兰氏阳性菌（包括耐药菌）的体外抗菌活性大约弱两到四倍。这些结果表明 L-脯氨酰-D-脯氨酸亚结构发挥了作用在观察到的三前肽素效力中发挥重要作用。