科研之友
微信
新浪微博
Facebook
分享链接
摘要
Functional insights into bioactive natural products with medicinal potential are often hindered by their structural complexity. We herein report a simplified model system to investigate the functional significance of a structural motif of biologically potent muraymycin antibiotics of the A-series. These compounds have a highly unusual omega-guanidinylated fatty acid moiety, which has been proposed to mediate membrane penetration, thus enabling the interaction of A-series muraymycins with their intracellular target MraY. Our assay was based on a synthetic conjugate of this fatty acid structure with a negatively charged fluorophore lacking membrane permeability. Using this conjugate, immobilised giant unilamellar lipid vesicles and confocal laser scanning fluorescence microscopy, we demonstrated that the attachment of the omega-N-hydroxyguanidinyl fatty acid unit led to an enhanced uptake of the fluorophore into the vesicles. This represents the first experimental evidence of this unusual structural motif's functional relevance for the parent natural product, which may support the future design of novel muraymycin analogues.
- 出版日期2015
