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

Feglymycin对细菌细胞壁生物合成作用机制的研究

• 批准号: 237444298
• 负责人: Professor Dr. Roderich D. Süßmuth
• 金额: --
• 依托单位: Arbeitsgruppe Biologische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/237444298?language=en
• 关键词: Investigations; mode; action; feglymycin; bacterial

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.

线性13 MER肽FeGlymycin由非蛋白质生成氨基酸4-羟基苯基甘氨酸和3,5-二羟基苯基甘氨酸组成。它具有针对高病毒的显着活性，对耐甲氧西林的金黄色葡萄球菌菌株（MRSA）具有非常好的抗菌活性。完善总合成后，我们确定了细菌细胞壁合成的可能靶标，Mura和Murc酶。因此，我们从合成的femforment上构成了feglymycin的完整Ala-Scan扫描。对酶和体外的13种Ala-feglycins的生物测试导致氨基酸对生物活性的不同贡献。我们打算对Feglymycin的分子靶标进行研究，特别是由合成标记作为光标记和荧光标签的支持。 ProteOMC方法将进一步支持此Apporach。我们打算在溶液中结构feglymycin并与蛋白质靶标结合。这项工作将对评估Feglymycin作为肽药物的潜力产生重大影响。

项目成果

Alanine Scan of the Peptide Antibiotic Feglymycin: Assessment of Amino Acid Side Chains Contributing to Antimicrobial Activity

• DOI: 10.1002/cbic.201300032
• 发表时间: 2013-03-18
• 期刊: CHEMBIOCHEM
• 影响因子: 3.2
• 作者: Haenchen, Anne;Rausch, Saskia;Suessmuth, Roderich D.
• 通讯作者: Suessmuth, Roderich D.

Biosynthesis of the Peptide Antibiotic Feglymycin by a Linear Nonribosomal Peptide Synthetase Mechanism

• DOI: 10.1002/cbic.201500432
• 发表时间: 2015-12-14
• 期刊: CHEMBIOCHEM
• 影响因子: 3.2
• 作者: Gonsior, Melanie;Muhlenweg, Agnes;Suessmuth, Roderich D.
• 通讯作者: Suessmuth, Roderich D.