Rotem Shahar, Mor Amram
Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Israel.
Biochim Biophys Acta. 2009 Aug;1788(8):1582-92. doi: 10.1016/j.bbamem.2008.10.020. Epub 2008 Nov 5.
The relatively recent recognition of the major role played by antimicrobial peptides (AMPs) in sustaining an effective host response to immune challenges was greatly influenced by studies of amphibian peptides. AMPs are also widely regarded as a potential source of future antibiotics owing to a remarkable set of advantageous properties ranging from molecular simplicity to low-resistance swift-kill of a broad range of microbial cells. However, the peptide formula per se, represents less than ideal drug candidates, namely because of poor bioavailability issues, potential immunogenicity, optional toxicity and high production costs. To address these issues, synthetic peptides have been designed, reproducing the critical peptide biophysical characteristic in unnatural sequence-specific oligomers. Thus, the use of peptidomimetics to overcome the limitations inherent to peptides physical characteristics is becoming an important and promising approach for improving the therapeutic potential of AMPs. Here, we review most recent advances in the design strategies and the biophysical properties of the main classes of mimics to natural AMPs, emphasizing the importance of structure-activity relationship studies in fine-tuning of their physicochemical attributes for improved antimicrobial properties.
抗菌肽（AMPs）在维持宿主对免疫挑战的有效应答中发挥的主要作用，是相对近期才被认识到的，这在很大程度上受到对两栖类动物肽研究的影响。由于抗菌肽具有一系列显著的优势特性，从分子结构简单到能快速杀死多种微生物细胞且耐药性低，它们也被广泛视为未来抗生素的潜在来源。然而，肽本身并不完全是理想的药物候选物，这主要是因为存在生物利用度差、潜在免疫原性、选择性毒性以及生产成本高等问题。为了解决这些问题，人们设计了合成肽，在非天然的序列特异性低聚物中重现关键的肽生物物理特性。因此，使用肽模拟物来克服肽物理特性固有的局限性，正成为提高抗菌肽治疗潜力的一种重要且有前景的方法。在此，我们综述了天然抗菌肽主要类别模拟物的设计策略和生物物理特性方面的最新进展，强调了构效关系研究在微调其物理化学属性以改善抗菌特性方面的重要性。
