Department of Biosciences and Informatics, Keio University, 3-14-1 Hiyoshi, Kouhoku-ku, Yokohama 223-8522, Japan.
Chem Soc Rev. 2022 Oct 3;51(19):8160-8173. doi: 10.1039/d2cs00470d.
Glycoconjugates on animal cell surfaces are involved in numerous biological functions and diseases, especially the adhesion/metastasis of cancer cells, infection, and the onset of glycan-related diseases. In addition to glycoantigen detection, the regulation of glycan (carbohydrate)-protein interactions is needed to develop therapeutic strategies for glycan-related diseases. Preparation of a diverse range of glycan derivatives requires a massive effort, but the preparation and identification of alternative glycan-mimetic peptide mimotopes may provide a solution to this issue. Peptide mimotopes are recognized by glycan-binding proteins, such as lectins, enzymes, and antibodies, alternative to glycan ligands. Phage-display technology is the first choice in the selection of "glycan (carbohydrate)-mimetic peptide mimotopes" from a large repertoire of library sequences. This tutorial review describes the advantages of peptide mimotopes in comparison to glycan ligands, as well as their structural and functional mimicry. The detailed library design is followed by a description of the strategy used to improve affinity, and finally, an outline of the vaccine application of glycan-mimetic peptides is provided.
动物细胞表面的糖缀合物参与了许多生物功能和疾病,特别是癌细胞的黏附和转移、感染以及糖相关疾病的发生。除了糖抗原检测外,还需要调控糖(碳水化合物)-蛋白相互作用,以开发糖相关疾病的治疗策略。制备各种糖衍生物需要大量的努力,但制备和鉴定替代糖类似肽模拟物可能是解决这个问题的一种方法。糖结合蛋白(如凝集素、酶和抗体)识别的肽模拟物是糖配体的替代物。噬菌体展示技术是从文库序列中选择“糖(碳水化合物)-模拟肽模拟物”的首选方法。本教程综述描述了与糖配体相比,肽模拟物的优势,以及它们的结构和功能模拟。详细介绍了文库设计,然后描述了提高亲和力的策略,最后概述了糖模拟肽的疫苗应用。