Mousa Walaa K, Shaikh Ashif Y, Ghemrawi Rose, Aldulaimi Mohammed, Al Ali Aya, Sammani Nour, Khair Mostafa, Helal Mohamed I, Al-Marzooq Farah, Oueis Emilia
College of Pharmacy, Al Ain University PO BOX 64141 Abu Dhabi United Arab Emirates
AAU Health and Biomedical Research Center, Al Ain University PO BOX 112612 Abu Dhabi United Arab Emirates.
RSC Med Chem. 2024 Oct 28;16(1):312-23. doi: 10.1039/d4md00383g.
The prevalence of antibacterial resistance has become one of the major health threats of modern times, requiring the development of novel antibacterials. Antimicrobial peptides are a promising source of antibiotic candidates, mostly requiring further optimization to enhance druggability. In this study, a series of new antimicrobial peptides derived from lactomodulin, a human microbiome natural peptide, was designed, synthesized, and biologically evaluated. Within the most active region of the parent peptide, linear peptide with the sequence LSKISGGIGPLVIPV-NH and its cyclic derivatives and showed strong antibacterial activity against Gram-positive bacteria, including resistant strains, and Gram-negative bacteria. The peptides were found to have a rapid onset of bactericidal activity and transmission electron microscopy clearly shows the disintegration of the cell membrane, suggesting a membrane-targeting mode of action.
抗菌耐药性的流行已成为现代主要的健康威胁之一，这需要开发新型抗菌药物。抗菌肽是有前景的抗生素候选来源，大多需要进一步优化以提高成药性能。在本研究中，设计、合成并对一系列源自人微生物组天然肽乳调节素的新型抗菌肽进行了生物学评估。在亲本肽的最活跃区域内，序列为LSKISGGIGPLVIPV-NH的线性肽及其环化衍生物表现出对革兰氏阳性菌（包括耐药菌株）和革兰氏阴性菌的强抗菌活性。发现这些肽具有快速的杀菌活性，透射电子显微镜清楚地显示了细胞膜的解体，表明其作用模式为靶向细胞膜。
