Recent technological advancements, including computer-assisted drug discovery, gene-editing techniques, and high-throughput screening approaches, have greatly expanded the palette of methods for the discovery of peptides available to researchers. These emerging strategies, driven by recent advances in bioinformatics and multi-omics, have significantly improved the efficiency of peptide drug discovery when compared with traditional in vitro and in vivo methods, cutting costs and improving their reliability. An added benefit of peptide-based drugs is the ability to precisely target protein-protein interactions, which are normally a particularly challenging aspect of drug discovery. Another recent breakthrough in this field is targeted protein degradation through proteolysis-targeting chimeras. These revolutionary compounds represent a noteworthy advancement over traditional small-molecule inhibitors due to their unique mechanism of action, which allows for the degradation of specific proteins with unprecedented specificity. The inclusion of a peptide as a protein-of-interest-targeting moiety allows for improved versatility and the possibility of targeting otherwise undruggable proteins. In this review, we discuss various novel wet-lab and computational multi-omic methods for peptide drug discovery, provide an overview of therapeutic agents discovered through these cutting-edge techniques, and discuss the potential for the therapeutic delivery of peptide-based drugs.

中文翻译：

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肽药物发现的最新进展：新策略和靶向蛋白质降解。


最近的技术进步，包括计算机辅助药物发现、基因编辑技术和高通量筛选方法，极大地扩展了研究人员可用的肽发现方法库。与传统的体外和体内方法相比，这些新兴策略在生物信息学和多组学最新进展的推动下，显著提高了多肽药物发现的效率，降低了成本并提高了其可靠性。基于肽的药物的另一个好处是能够精确靶向蛋白质-蛋白质相互作用，这通常是药物发现中一个特别具有挑战性的方面。该领域的另一个最新突破是通过蛋白水解靶向嵌合体进行靶向蛋白质降解。这些革命性的化合物代表了传统小分子抑制剂的显着进步，因为它们具有独特的作用机制，能够以前所未有的特异性降解特定蛋白质。将肽作为目标蛋白靶向部分可以提高多功能性，并有可能靶向其他不可成药的蛋白质。在这篇综述中，我们讨论了用于肽药物发现的各种新型湿实验室和计算多组学方法，概述了通过这些尖端技术发现的治疗剂，并讨论了基于肽的药物的治疗递送的潜力。