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

该线状13聚体多肽非蛋白原性氨基酸4-羟基苯甘氨酸和3，5-二羟基苯甘氨酸组成。它对HI病毒有显著的抗病毒活性，对耐甲氧西林金黄色葡萄球菌(MRSA)有很好的抗菌活性。在完成总合成后，我们确定了细菌细胞壁合成的可能靶点，Mura和MurC酶。因此，我们合成了非淋霉素的全ALA扫描。通过对13种丙氨酸-非淋菌素的生物活性测定和体外活性测定，发现氨基酸对生物活性的贡献不同。我们打算对非淋霉素的分子靶标进行研究，特别是在合成标记如光标记和荧光标记的支持下。这一分配将得到蛋白质组方法的进一步支持。我们打算在溶液中结合非淋霉素的结构和结合蛋白质靶标。这项工作将对评价非淋霉素作为多肽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.