Molecular and Biological Agricultural Science Program, Taiwan International Graduate Program, Academia Sinica, Taipei, 11529, Taiwan; Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, 402, Taiwan.
Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd, Jiaushi, Ilan, 262, Taiwan; The iEGG and Animal Biotechnology Center and the Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, 402, Taiwan.
Eur J Med Chem. 2023 Nov 5;259:115680. doi: 10.1016/j.ejmech.2023.115680. Epub 2023 Jul 25.
The growing prevalence of antimicrobial resistance (AMR) has brought with it a continual increase in the numbers of deaths from multidrug-resistant (MDR) infections. Since the current arsenal of antibiotics has become increasingly ineffective, there exists an urgent need for discovery and development of novel antimicrobials. Antimicrobial peptides (AMPs) are considered to be a promising class of molecules due to their broad-spectrum activities and low resistance rates compared with other types of antibiotics. Since AMPs also often play major roles in elevating the host immune response, the molecules may also be called "host defense peptides." Despite the great promise of AMPs, the majority remain unsuitable for clinical use due to issues of structural instability, degradation by proteases, and/or toxicity to host cells. Moreover, AMP activities in vivo can be influenced by many factors, such as interaction with blood and serum biomolecules, physiological salt concentrations or different pH values. To overcome these limitations, structural modifications can be made to the AMP. Among several modifications, physical and chemical conjugation of AMP to other biomolecules is widely considered an effective strategy. In this review, we discuss structural modification strategies related to conjugation of AMPs and their possible effects on mode of action. The conjugation of fatty acids, glycans, antibiotics, photosensitizers, polymers, nucleic acids, nanoparticles, and immobilization to biomaterials are highlighted.
抗菌药物耐药性（AMR）的不断增加导致了多药耐药（MDR）感染的死亡人数持续增加。由于目前的抗生素库越来越无效，因此迫切需要发现和开发新型抗菌药物。抗菌肽（AMPs）由于其广谱活性和与其他类型抗生素相比较低的耐药率，被认为是一类很有前途的分子。由于 AMPs 还常常在提高宿主免疫反应方面发挥重要作用，因此这些分子也可以被称为“宿主防御肽”。尽管 AMP 具有巨大的应用前景，但由于结构不稳定、蛋白酶降解以及对宿主细胞的毒性等问题，大多数 AMP 仍不适合临床应用。此外，AMP 在体内的活性可能受到许多因素的影响，例如与血液和血清生物分子的相互作用、生理盐浓度或不同的 pH 值。为了克服这些限制，可以对 AMP 进行结构修饰。在几种修饰方法中，将 AMP 与其他生物分子进行物理和化学偶联被广泛认为是一种有效的策略。在这篇综述中，我们讨论了与 AMP 偶联相关的结构修饰策略及其对作用模式的可能影响。重点介绍了脂肪酸、聚糖、抗生素、光敏剂、聚合物、核酸、纳米颗粒和固定在生物材料上的偶联。
