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-aminophenyl)-10,15,20-tri(4-N-methylpyridyl)-21H,23H-porphyrin using a thiol–maleimide “click” coupling. The peptide-coupled photosensitizer has demonstrated an improved PACT efficiency compared to the cationic porphyrin alone. This enhancement has been observed against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli in particular. Flow cytometry analyses and confocal imaging microscopy demonstrated that the porphyrin–peptide conjugate selectively adhered to the cell walls of either Gram-positive or Gram-negative bacteria, thus justifying the damages induced by singlet oxygen production.

中文翻译：

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附着多粘菌素B后阳离子卟啉的增强的杀菌和靶向性能

与在光动力抗微生物化学疗法（PACT）中被认为是有效的光敏剂的普通阳离子卟啉相比，已经合成了一种新的化合物，该化合物由与多粘菌素B的衍生物共价连接的阳离子卟啉组成，并具有增强的活性和靶向特性。建立了合成途径来保留该肽的杀菌活性。因此，N末端氨基酸（升多粘菌素B（PMB）的-2,4-二氨基丁酸）被切换为半胱氨酸残基。然后，将所得的PMB衍生物共价键合至5-（4-氨基苯基）-10,15,20-tri（4- N-甲基吡啶基）-21H，23H-卟啉，使用硫醇-马来酰亚胺“喀哒”键。与单独的阳离子卟啉相比，肽偶联的光敏剂具有更高的PACT效率。尤其是针对金黄色葡萄球菌，铜绿假单胞菌和大肠杆菌观察到了这种增强。流式细胞仪分析和共聚焦显微镜检查表明，卟啉-肽结合物选择性地粘附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害。