通过酶可移除的N-终端溶解标签合成胰岛素-desB30类似物
Yuankun Dao1, Terra Lin1, Ngoc Le Bich Tran1
1Department of Pediatrics, Division of Diabetes and Endocrinology, Stanford University, Palo Alto, California 94304, United States.
Organic letters
|November 13, 2025
概括
我们开发了一种新型的胰岛素类似物化学合成方法,通过使用临时的聚氨酸标签来提高胰岛素A链的可溶性. 这种精简的过程提高了胰岛素生产效率和纯度.
科学领域:
- 生物化学 生物化学
- 有机化学 有机化学
- 药用化学 医学化学
背景情况:
- 化学合成为新型胰岛素类似物提供了一条途径.
- 胰岛素A链的溶解性是合成效率的一个主要瓶.
研究的目的:
- 开发一种精简的化学合成胰岛素类似物.
- 为了克服胰岛素A链的可溶性限制.
主要方法:
- 直接Fmoc-SPPS (固相合成) 的胰岛素A链.
- 使用了一个临时的聚氨酸溶解度标签.
- 在温和的水性条件下使用Lys-C去除标签.
主要成果:
- 实现了胰岛素A链的更好的隔离,折叠和链组合.
- 已证明适用于具有挑战性的胰岛素标,包括突变体和代孕物.
- 交付的高纯度胰岛素类似产品.
结论:
- 聚氨酸标签策略显著增强了胰岛素模拟合成.
- 这种方法提供了一种通用而有效的途径,可以达到复杂的胰岛素点.
- 这种方法有助于生产高纯度胰岛素类似物.
相关概念视频
Insulin: Biosynthesis, Chemistry, and Preparation
1.2K
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
1.2K
Insulin Secretory Vesicles
6.4K
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
6.4K
Tagging and Fusion Proteins
8.3K
Proteins are involved in several cellular processes and biochemical reactions. Analyzing a specific protein of interest requires it to be isolated from the other proteins in the cell. This is achieved by overexpressing the specific gene in a suitable host to produce large quantities of the target protein. A tag or label is recombined with the gene to produce a fusion protein containing the target protein and the tag. The tags on these fusion proteins can then be used for easy detection and...
8.3K
Insulin Formulations: Types and Delivery
632
Insulin preparations are categorized by their duration of action into short-acting and long-acting types. Two strategies are used to modify insulin's absorption and pharmacokinetic profile: slowing the absorption post-subcutaneous injection, or altering human insulin's amino acid sequence or protein structure. These changes retain the insulin's ability to bind to the insulin receptor, but alter its behavior in solution or after injection.
Short-acting insulins are divided into...
Short-acting insulins are divided into...
632


