Enhanced Photobactericidal and Targeting Properties of a Cationic Porphyrin following the Attachment of Polymyxin B
Enhanced Photobactericidal and Targeting Properties of a Cationic Porphyrin following the Attachment of Polymyxin B
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DOI：
10.1021/acs.bioconjchem.7b00516
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发表时间：
2017-09-01
影响因子：
4.7
通讯作者：
Ouk, Tan-Sothea
中科院分区：
文献类型：
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作者：
Le Guern, Florent;Sol, Vincent;Ouk, Tan-Sothea
合成了一种由阳离子卟啉共价连接到多粘菌素B衍生物上的新型化合物，与通常被认为是光动力抗菌化疗(PACT)中有效光敏剂的阳离子卟啉相比，具有更高的活性和靶向性。建立了一条合成途径来保存该多肽的杀菌活性。相应地，多粘菌素B的N端氨基酸(L-2，4-二氨基丁酸)被替换为半胱氨酸残基。然后，通过硫醇马来酰亚胺“点击”偶联，将得到的PMB衍生物共价结合到5-(4-aminopheny1)-10，15，20-tri(4-Nmethylpyridy1)-21H，23H-porphyrin上。多肽偶联光敏剂显示出比阳离子卟啉单独的PACT效率更高的PACT效率，这种增强是共聚焦观察到的。特别是对金黄色葡萄球菌、铜绿假单胞菌和大肠杆菌。流式细胞仪和图像显微镜分析表明，卟啉多肽结合物选择性地附着在革兰氏阳性或革兰氏阴性细菌的细胞壁上，从而证明了单线态氧产生所造成的损伤是合理的。
A novel compound consisting of a cationic porphyrin covalently attached to a derivative of polymyxin B has been synthesized and presents enhanced activity and targeting properties compared to the usual cationic porphyrins recognized as efficient photosensitizers in photodynamic antimicrobial chemotherapy (PACT). A synthesis pathway was established to preserve the bactericidal activity of the peptide. Accordingly, the N-terminal amino acid (L-2,4-diaminobutyric acid) of polymyxin B (PMB) was switched for a cysteine residue. Then, the resulting derivative of PMB was covalently bound to 5-(4-aminopheny1)-10,15,20-tri(4-Nmethylpyridy1)-21H,23H-porphyrin using a thiol maleimide "click" coupling. peptide-coupled photosensitizer has demonstrated an improved PACT efficiency compared to the cationic porphyrin alone This enhancement has been observed confocal. against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli in particular. Flow cytometry analyses and imaging microscopy demonstrated that the porphyrin peptide conjugate selectively adhered to the cell walls of either Grain positive or Gram-negative bacteria, thus justifying the damages induced by singlet oxygen production.