School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Department of Chemistry, Biomedical Engineering, Macromolecular Science and Engineering, Michigan Neuroscience Institute, The University of Michigan, Ann Arbor, MI 48109, USA.
Biomolecules. 2024 Mar 8;14(3):320. doi: 10.3390/biom14030320.
Antimicrobial peptides (AMPs), as well as host defense peptides (HDPs), constitute the first line of defense as part of the innate immune system. Humans are known to express antimicrobial precursor proteins, which are further processed to generate AMPs, including several types of α/β defensins, histatins, and cathelicidin-derived AMPs like LL37. The broad-spectrum activity of AMPs is crucial to defend against infections caused by pathogenic bacteria, viruses, fungi, and parasites. The emergence of multi-drug resistant pathogenic bacteria is of global concern for public health. The prospects of targeting antibiotic-resistant strains of bacteria with AMPs are of high significance for developing new generations of antimicrobial agents. The 37-residue long LL37, the only cathelicidin family of AMP in humans, has been the major focus for the past few decades of research. The host defense activity of LL37 is likely underscored by its expression throughout the body, spanning from the epithelial cells of various organs-testis, skin, respiratory tract, and gastrointestinal tract-to immune cells. Remarkably, apart from canonical direct killing of pathogenic organisms, LL37 exerts several other host defense activities, including inflammatory response modulation, chemo-attraction, and wound healing and closure at the infected sites. In addition, LL37 and its derived peptides are bestowed with anti-cancer and anti-amyloidogenic properties. In this review article, we aim to develop integrative, mechanistic insight into LL37 and its derived peptides, based on the known biophysical, structural, and functional studies in recent years. We believe that this review will pave the way for future research on the structures, biochemical and biophysical properties, and design of novel LL37-based molecules.
抗菌肽 (AMPs) 和宿主防御肽 (HDPs) 作为先天免疫系统的一部分，构成了第一道防线。人类已知表达抗菌前体蛋白，这些蛋白进一步被加工生成 AMPs，包括几种类型的 α/β 防御素、组蛋白和 cathelicidin 衍生的 AMPs，如 LL37。AMPs 的广谱活性对于抵御由致病性细菌、病毒、真菌和寄生虫引起的感染至关重要。多药耐药性致病细菌的出现引起了全球公共卫生的关注。用 AMPs 靶向抗生素耐药菌株的前景对于开发新一代抗菌药物具有重要意义。37 个残基长的 LL37 是人类唯一的 cathelicidin 家族 AMP，过去几十年的研究主要集中在它身上。LL37 的宿主防御活性可能是由其在全身的表达所强调的，从各种器官的上皮细胞（睾丸、皮肤、呼吸道和胃肠道）到免疫细胞。值得注意的是，除了对致病性生物的直接杀伤作用外，LL37 还具有其他几种宿主防御活性，包括炎症反应调节、趋化作用以及感染部位的伤口愈合和闭合。此外，LL37 及其衍生肽具有抗癌和抗淀粉样变性的特性。在这篇综述文章中，我们旨在根据近年来已知的生物物理、结构和功能研究，对 LL37 及其衍生肽进行综合的、机制性的深入了解。我们相信，这篇综述将为未来关于 LL37 结构、生化和生物物理特性以及新型基于 LL37 的分子的设计的研究铺平道路。
