Faculty of Pharmacy, PHENIKAA University, Hanoi 12116, Vietnam.
PHENIKAA Institute for Advanced Study (PIAS), PHENIKAA University, Hanoi 12116, Vietnam.
J Med Chem. 2022 Feb 24;65(4):3026-3045. doi: 10.1021/acs.jmedchem.1c01744. Epub 2022 Feb 3.
The threats of drug resistance and new emerging pathogens have led to an urgent need to develop alternative treatment therapies. Recently, considerable research efforts have focused on membrane-active peptides (MAPs), a category of peptides in drug discovery with antimicrobial, anticancer, and cell penetration activities that have demonstrated their potential to be multifunctional agents. Nonetheless, natural MAPs have encountered various disadvantages, which mainly include poor bioavailability, the lack of a secondary structure in short peptides, and high production costs for long peptide sequences. Hence, an "all-hydrocarbon stapling system" has been applied to these peptides and proven to effectively stabilize the helical conformations, improving proteolytic resistance and increasing both the potency and the cell permeability. In this review, we summarized and categorized the advances made using this powerful technique in the development of stapled MAPs. Furthermore, outstanding issues and suggestions for future design within each subcategory were thoroughly discussed.
耐药性和新出现的病原体的威胁导致人们迫切需要开发替代治疗方法。最近，大量研究工作集中在膜活性肽（MAPs）上，这是一类具有抗菌、抗癌和细胞穿透活性的药物发现肽，已证明其具有多功能药物的潜力。然而，天然 MAPs 遇到了各种缺点，主要包括生物利用度差、短肽中缺乏二级结构以及长肽序列的高生产成本。因此，一种“全碳氢化合物订书钉系统”已应用于这些肽，并被证明能有效地稳定螺旋构象，提高抗蛋白水解能力，并提高效力和细胞通透性。在这篇综述中，我们总结和分类了使用这种强大技术在订书钉 MAPs 开发方面的进展。此外，还深入讨论了每个子类中未来设计的突出问题和建议。
