College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam 52828, Korea.
College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam 50834, Korea.
Toxins (Basel). 2020 May 10;12(5):313. doi: 10.3390/toxins12050313.
Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.
从两栖动物皮肤分泌物中衍生的毒素肽具有独特的降血糖活性。这些肽中有许多具有阳离子性和两亲性的结构相似性，似乎具有细胞穿透能力。它们的胰岛素促分泌作用机制尚未阐明，但它们在调节动物模型中的血糖水平方面显示出巨大的潜力。因此，它们作为治疗 2 型糖尿病的潜在药物候选物而出现。尽管具有抗糖尿病活性，但在临床应用方面仍存在需要解决的药物挑战。在这里，我们概述了与从两栖动物皮肤分泌物中衍生的毒素衍生抗糖尿病肽相关的最新研究。在后一部分，我们介绍了其体内传递的瓶颈挑战以及可能适用于延长其血液循环时间的一般药物传递策略。我们将研究重点放在已成功应用于改善临床可用的毒素衍生抗糖尿病肽药物 exendin-4 的血浆半衰期的策略上。
