Xie Xiayang, Gao Lixia, Shull Austin Y, Teng Yong
Department of Pediatrics, Emory Children's Center, Emory University, Atlanta, GA 30322, USA.
Department of Oral Biology, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.
Future Med Chem. 2016 Oct;8(16):1969-1980. doi: 10.4155/fmc-2016-0102. Epub 2016 Sep 21.
Peptide-based drug discovery has experienced a remarkable resurgence within the past decade due to the emerging class of inhibitors known as stapled peptides. Stapled peptides are therapeutic protein mimetics that have been locked within a specific conformational structure by hydrocarbon stapling. These peptides are highly important in selectively impairing disease-relevant protein-protein interactions and exhibit significant pharmacokinetic advantages over other forms of therapeutics in terms of affinity, specificity, size, synthetic accessibility and resistance to proteolytic degradation. A series of stapled peptides are currently in development, and the potential successes of these peptides, either as single-agent treatments or as combinational treatments with other therapeutic modalities, could potentially change the landscape of protein therapeutic development. Here, we provide examples of successful discovery efforts to illustrate the research strategies of stapled peptides in drug design and development.
在过去十年中，由于被称为环肽的新型抑制剂的出现，基于肽的药物发现经历了显著复兴。环肽是一种治疗性蛋白质模拟物，通过烃链环化被锁定在特定的构象结构中。这些肽在选择性破坏与疾病相关的蛋白质-蛋白质相互作用方面非常重要，并且在亲和力、特异性、大小、合成可及性和抗蛋白水解降解方面比其他形式的治疗剂具有显著的药代动力学优势。目前有一系列环肽正在研发中，这些肽作为单一药物治疗或与其他治疗方式联合治疗的潜在成功，可能会改变蛋白质治疗开发的格局。在此，我们提供成功发现的实例，以说明环肽在药物设计和开发中的研究策略。
