Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St., 16/10, Moscow 117997, Russia.
St. Petersburg Research Institute of Phthisiopulmonology, Ligovskii Prospect, 2-4, St. Petersburg 191036, Russia.
Int J Mol Sci. 2024 May 6;25(9):5042. doi: 10.3390/ijms25095042.
Peptides show high promise in the targeting and intracellular delivery of next-generation biotherapeutics. The main limitation is peptides' susceptibility to proteolysis in biological systems. Numerous strategies have been developed to overcome this challenge by chemically enhancing the resistance to proteolysis. In nature, amino acids, except glycine, are found in L- and D-enantiomers. The change from one form to the other will change the primary structure of polypeptides and proteins and may affect their function and biological activity. Given the inherent chiral nature of biological systems and their high enantiomeric selectivity, there is rising interest in manipulating the chirality of polypeptides to enhance their biomolecular interactions. In this review, we discuss the first examples of up-and-down homeostasis regulation by two enantiomeric drugs: immunostimulant Thymogen (L-Glu-L-Trp) and immunosuppressor Thymodepressin (D-Glu(D-Trp)). This study shows the perspective of exploring chirality to remove the chiral wall between L- and D-biomolecules. The selected clinical result will be discussed.
肽在靶向和细胞内递送上一代生物治疗药物方面显示出巨大的潜力。主要的限制是肽在生物系统中易被蛋白水解。为了克服这一挑战，人们已经开发了许多策略，通过化学方法增强对蛋白水解的抗性。在自然界中，除了甘氨酸外，所有的氨基酸都以 L-和 D-对映异构体的形式存在。从一种形式转变为另一种形式将改变多肽和蛋白质的一级结构，并可能影响它们的功能和生物活性。鉴于生物系统固有的手性性质及其对映体的高选择性，人们对手性多肽的手性操纵以增强其生物分子相互作用的兴趣日益浓厚。在这篇综述中，我们讨论了两种对映体药物（免疫刺激剂胸腺生成素（L-Glu-L-Trp）和免疫抑制剂胸腺肽（D-Glu(D-Trp)））上下稳态调节的第一个例子。这项研究展示了探索手性以消除 L-和 D-生物分子之间手性壁的前景。将讨论选定的临床结果。
