Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 151-742, Korea.
Expert Rev Anti Infect Ther. 2014 Dec;12(12):1477-86. doi: 10.1586/14787210.2014.976613. Epub 2014 Nov 5.
The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.
越来越多的多药耐药病原体的出现,使得人们迫切需要合适的替代品来替代目前的抗生素。抗菌肽(AMPs)作为抵御微生物的防御武器而受到广泛关注,因为它们具有广谱活性、独特的作用机制和罕见的抗生素耐药变体。尽管具有理想的特性,但由于毒性、稳定性和制造成本等问题,它们在药物开发方面表现出了局限性。由于这些缺点,只有少数几种 AMP 已在 III 期临床试验中进行了测试,并且没有任何 AMP 获得美国 FDA 的批准。然而,通过改变物理化学特性和引入非天然氨基酸、乙酰化或酰胺化等众所周知的方法,以及分子靶向 AMPs、脂质体制剂和药物传递系统等现代技术,可以克服这些障碍。因此,目前该领域的挑战是开发具有合理成本的治疗性 AMPs,并克服其局限性。