Novel Inhibitors of Peptidoglycan Biosynthesis Targeting Gram-positive Pathogens

描述（由申请人提供）：拟议的研究涉及合成和研究具有优异生物活性的脂降肽抗生素，以对抗革兰氏阳性阳性细菌，包括有问题的耐药病原体。研究中的脂降肽抗生素被认为是通过抑制转糖基化反应来表现其生物活性的，而转糖基化反应是肽聚糖生物合成途径中一个关键的后期转化。此外，抑制脂质循环也可能有助于观察到的生物活性。拟议的研究旨在确定新的化学实体，用于治疗革兰氏阳性感染，特别是由于有问题的耐药革兰氏阳性病原体引起的感染。

DESCRIPTION (provided by applicant): The proposed research involves synthesis and study of lipodepsipeptide antibiotics that possess excellent biological activity versus Gram-positive positive bacteria, including problematic resistant pathogens. The lipodepsipeptide antibiotics under study are believed to manifest their biological activity through inhibition of the transglycosylation reaction, a key late stage transformation in the peptidoglycan biosynthetic pathway. In addition, the inhibition of lipid recycling may also contribute to the observed biological activity. The proposed research seeks to identify novel chemical entities to be used for the treatment of Gram-positive infections and, in particular, infections due to problematic resistant Gram-positive pathogens.