抗菌肽的非肽或小分子模拟物研究进展

Recent advances on non-peptide or small molecule mimics of antimicrobial peptides

抗生素耐药性成为21世纪最严重的公共卫生问题之一。各种耐药菌,特别是ESKAPE(耐药的肠球菌、金黄色葡萄球菌、克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌)的出现严重威胁了人类的健康。绝大部分传统抗生素作用于细菌表面或内部的特定靶点,容易产生耐药性。因此,急需研发新作用机制的抗菌药物解决抗生素耐药性问题。抗菌肽是自然界中广泛存在的多肽,在抗感染疾病的治疗中具有广阔的应用前景。尽管如此,天然抗菌肽存在一些缺陷,比如体内的代谢稳定性差、活性普遍不高、毒副作用以及生产成本较高等,限制了其应用。解决这些问题较为有效的途径之一就是根据抗菌肽的净正电荷性质及亲水亲脂的整体构象特征,设计合成抗菌肽的模拟物。近年来,抗菌肽的非肽或小分子模拟物研究发展快速。本文将对这一领域的研究进展进行详尽的综述。

Antibiotic resistance has become one of the most serious public health issues in the 21st century.The emergence of various drug-resistant bacteria,especially ESKAPE,has seriously threatened human health.Most traditional antibiotics act on specific targets on the surface or inside of bacteria and are prone to elicit drug resistance.Therefore,there is an urgent need to develop antibiotics with new mechanisms to combat antibiotic resistance.Antimicrobial peptides are ubiquitous in nature and show promising applications in the treatment of infectious diseases.Nevertheless,natural antimicrobial peptides have some drawbacks such as poor metabolic stability,low activity,toxic and side effects,and high production costs,which limit their applications.One of the effective approaches to overcome these problems is to design and synthesize mimics of antimicrobial peptides according to their net positive charge properties and the overall conformational characteristics of hydrophilic lipophiles.In recent years,rapid progress has been made in non-peptide or small-molecule mimics of antimicrobial peptides,and here we will summarize the recent advances on nonpeptide or small-molecule mimics of antimicrobial peptides in detail.