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肽体:弥合肽与抗体之间的差距。

Peptibodies: Bridging the gap between peptides and antibodies.

机构信息

Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Int J Biol Macromol. 2024 Oct;278(Pt 2):134718. doi: 10.1016/j.ijbiomac.2024.134718. Epub 2024 Aug 12.

DOI:10.1016/j.ijbiomac.2024.134718
PMID:39142490
Abstract

Peptides are a very critical class of pharmaceutical compounds that can control several signaling pathways and thereby affect many physiological and biochemical processes. Previous research suggests that both peptides and antibodies may serve as potent tools for research, diagnostics, vaccination, and therapeutics across diverse domains. The distinct attributes of peptides, like their profound tissue penetration, efficient cellular internalization, reduced immunogenicity, and adaptability to chemical modification, underscore their significance in biomedical applications. However, they also possess drawbacks such as lower affinity, poor absorption, low stability to proteolytic digestion, and rapid clearance. The advent of peptibodies is a significant advance that improves the limitations of both peptides and antibodies. Peptibodies, or Peptide-Fc fusions, represent a promising therapeutic modality comprising biologically active peptides fused to an Fc domain. The stability and efficacy of the peptide are enhanced by this fusion strategy, which overcomes some of the inherent limitations. Many peptibodies have been developed to treat conditions like cancer, diabetes, and lupus. Romiplostim and Dulaglutide are the only ones approved by the EMA and FDA, respectively. Given the growing significance of peptibodies in the pharmaceutical landscape, this investigation aims to explain key aspects encompassing the intrinsic properties of peptides, the intricacies of peptibody production, and their potential therapeutic applications.

摘要

肽是一类非常重要的药物化合物,能够调控多种信号通路,从而影响许多生理和生化过程。先前的研究表明,肽和抗体都可能成为不同领域的研究、诊断、疫苗接种和治疗的有力工具。肽的独特属性,如深度组织穿透性、高效细胞内化、较低免疫原性和对化学修饰的适应性,突出了它们在生物医学应用中的重要性。然而,它们也存在一些缺点,如亲和力较低、吸收不良、对蛋白水解消化的稳定性差和清除速度快。肽抗体的出现是一项重大进展,改善了肽和抗体的局限性。肽抗体,或肽-Fc 融合物,是一种有前途的治疗模式,由与 Fc 结构域融合的生物活性肽组成。这种融合策略增强了肽的稳定性和功效,克服了一些固有限制。已经开发出许多肽抗体来治疗癌症、糖尿病和狼疮等疾病。罗米司亭和度拉糖肽分别是唯一获得 EMA 和 FDA 批准的药物。鉴于肽抗体在药物领域的重要性日益增加,本研究旨在解释涵盖肽内在特性、肽抗体生产复杂性及其潜在治疗应用的关键方面。

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