Kasturiarachchi Jagath C
SLIIT, Malabe, Sri Lanka.
Arch Microbiol. 2025 Jan 2;207(1):21. doi: 10.1007/s00203-024-04227-6.
The development of new medicines with unique methods of antimicrobial action is desperately needed due to the emerging multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus. Therefore, antimicrobial peptoids have emerged as potential new antimicrobials. Thirteen peptoid analogues have been designed and synthesized via solid phase synthesis. These peptoids have undergone a biological analysis to determine the structure-activity relationships that define their antibacterial activity. Each peptoid is composed of nine repeating N-substituted glycine monomers (9-mer). The monomer units were synthesized with three distinct alkyl side chain lengths: four-carbon butyl monomers, six-carbon hexyl monomers, and eight-carbon octyl monomers. Out of 12 different peptoids, only one peptoid called Tosyl-Octyl-Peptoid (TOP) demonstrated significant broad-spectrum bactericidal activity. TOP kills bacteria under non-dividing and dividing conditions. The Minimum Inhibitory Concentrations values of TOP for Staphylococcus epidermidis, Escherichia coli and Klebsiella were 20 µM, whereas Methicillin-resistant Staphylococcus aureus and Methicillin-sensitive Staphylococcus aureus were 40 µM. The highest MIC values were observed for Pseudomonas aeruginosa at 80 µM. The selectivity ratio was calculated, by dividing the 10% haemolysis activity (5 mM) by the median of the MIC (50 µM) yielding a selective ratio for TOP as 100. This selective ratio is well above previously reported peptidomimetics selective ratio of around 20. TOP shows broad-spectrum bactericidal action in both dividing and non-dividing bacteria in co-culture systems and intracellular bacterial killing activity. These results add new information about the antimicrobial peptoids and aid in the future design of synthetic peptoids with increased therapeutic potential.
由于出现了多重耐药细菌，如耐甲氧西林金黄色葡萄球菌，迫切需要开发具有独特抗菌作用方式的新型药物。因此，抗菌类肽已成为潜在的新型抗菌剂。通过固相合成设计并合成了13种类肽类似物。这些类肽经过了生物学分析，以确定定义其抗菌活性的构效关系。每个类肽由九个重复的N-取代甘氨酸单体（9聚体）组成。单体单元是用三种不同的烷基侧链长度合成的：四碳丁基单体、六碳己基单体和八碳辛基单体。在12种不同的类肽中，只有一种名为甲苯磺酰基-辛基-类肽（TOP）的类肽表现出显著的广谱杀菌活性。TOP在非分裂和分裂条件下均可杀死细菌。TOP对表皮葡萄球菌、大肠杆菌和克雷伯菌的最低抑菌浓度值为20μM，而耐甲氧西林金黄色葡萄球菌和甲氧西林敏感金黄色葡萄球菌为40μM。铜绿假单胞菌的最高MIC值为80μM。通过将10%溶血活性（5 mM）除以MIC中位数（50μM）计算选择性比率，得出TOP的选择性比率为100。这个选择性比率远高于先前报道的类肽模拟物约20的选择性比率。TOP在共培养系统中的分裂和非分裂细菌中均表现出广谱杀菌作用以及细胞内细菌杀伤活性。这些结果为抗菌类肽增添了新信息，并有助于未来设计具有更高治疗潜力的合成类肽。
