Investigations of the mode of action of feglymycin on the bacterial cell wall biosynthesis

线性13 mer肽feglymycin由非蛋白氨基酸4-羟基苯基甘氨酸和3，5-二羟基苯基甘氨酸组成。它对HI病毒有显著的抑制作用，对耐甲氧西林金黄色葡萄球菌（MRSA）有很好的抗菌作用。在进行全合成后，我们鉴定了细菌细胞壁合成的可能靶标，酶MurA和MurC。因此，我们合成了一个完整的丙氨酸扫描的feglymycin。对13种丙氨酸-feglymycin进行了体外生物学试验，结果表明氨基酸对生物活性的贡献不同。我们打算对feglymycin的分子靶点进行研究，特别是通过合成标记作为光标记和荧光标记来支持。蛋白质组学方法将进一步支持这一方法。我们打算在溶液中和蛋白质结合的feglymycin的结构。这项工作将对评估feglymycin作为肽类药物的潜力产生重大影响。

The linear 13 mer Peptide feglymycin is composed of non-proteinogenic amino acids 4-hydroxyphenyl glycine and 3,5-dihydroxyphenylglycine. It has a remarkable activity against the HI-virus and a very good antibacterial acitivy against methicillin-resistant Staphylococcus aureus strains (MRSA). After perfroming the total synthesis we identified possible targets of the bacterial cell wall synthesis, the enzymes MurA and MurC. Hence, we synthetically peformed a full Ala-scan of feglymycin. The biological testing of 13 Ala-feglymycins against the enzymes and in vitro resulted in different contributions of amino acids to bioactivity. We intend performing studies on the molecular targets of feglymycin, particularly supported by synthetic labels as photolabels and fluorescence labels. This apporach will be further supported by proteomc approaches. We intend to structures of feglymycin in solutions and bound to protein targets. This work will have a a significant impact on evaluating feglymycin for its potential as a peptide drug.