GlyTech, Inc., 134 Chudoji Minamimachi KRP #1-2F, Shimogyo-ku, Kyoto, 600-8813, Japan.
Otsuka Chemical Co., Ltd., 463 Kagasuno, Kawauchi-cho, Tokushima, 771-0193, Japan.
Chemistry. 2023 Jun 2;29(31):e202300111. doi: 10.1002/chem.202300111. Epub 2023 Apr 21.
Somatostatin (somatotropin release-inhibiting factor, SRIF) is a growth hormone inhibitory factor in the form of a 14- or 28-amino acid peptide. SRIF affects several physiological functions through its action on five distinct SRIF receptor subtypes (sst1-5). Native SRIF has only limited clinical applications due to its rapid degradation in plasma. To overcome this obstacle, we have developed glycosylated SRIF analogues that possess not only metabolic stability but also high affinity to all five receptor subtypes by attaching human complex-type oligosaccharides. Such glycosylated SRIF analogues with improved pharmacokinetic profiles could be potent and novel therapeutic drugs for SRIF-related diseases in which several SRIF receptor subtypes are closely involved, and also shed light on new indications. Our results show that chemical glycosylation can be a powerful tool for the development of peptide and protein analogues superior to the original molecules with enhanced drug properties.
生长抑素（生长激素释放抑制因子，SRIF）是一种 14 或 28 个氨基酸组成的肽类激素，作为生长激素抑制因子。SRIF 通过作用于五个不同的 SRIF 受体亚型（sst1-5）影响多种生理功能。由于其在血浆中迅速降解，天然 SRIF 的临床应用有限。为了克服这一障碍，我们通过连接人源复杂型寡糖，开发了具有代谢稳定性的糖基化 SRIF 类似物，并且对所有五个受体亚型均具有高亲和力。这些具有改善的药代动力学特征的糖基化 SRIF 类似物可以成为与多种 SRIF 受体亚型密切相关的 SRIF 相关疾病的有效且新颖的治疗药物，也为新的适应症提供了思路。我们的研究结果表明，化学糖基化可以成为开发优于原始分子的肽和蛋白质类似物的有力工具，这些类似物具有增强的药物特性。
