ディスクレート,キラルポリマー-インスリン結合体
Wencong Wang1, Yivan Jiang1, Zhihao Huang1
1Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Journal of the American Chemical Society
|September 20, 2022
まとめ
Iterative Exponential Growth (IEG) を使用して合成された精密なポリマー-タンパク質結合物は,薬物の投与に対する改善された制御を提供します. これらの新しいインスリン結合体は,糖尿病のマウスの血糖反応を最適化するために調整可能な性質を示しています.
科学分野:
- 生物結合化学
- ポリマー科学
- 薬理学について
背景:
- ポリマー結合は,治療用バイオマクロモレキュルの安定性と薬動性を高めます.
- 従来の方法は,製造の可変性および構造特性制御が制限されている異質な結合物を生成します.
研究 の 目的:
- 離散型キラルポリマーを用いたポリマー-タンパク質結合体の正確な合成戦略を開発する.
- 調節可能なポリマーの特徴がインスリン結合体の生物学的性能に与える影響を評価する.
主な方法:
- イテレティブ指数関数成長 (IEG) による離散型キラルポリマーの合成.
- モデル治療用ポリペプチドとしてインスリンにIEGポリマーを結合する.
- 糖尿病のマウスにおける血糖反応のインビオ評価は,PEGYlated インスリンとLantusと比較した.
主要な成果:
- IEG-インスリン結合剤は,ポリマーの分散性とヒラリティに関連した製造の変動性を排除しました.
- 調節可能なポリマーの特徴は,形状の硬さ,タンパク質の機能の調節などで,より速くまたは長期にわたるグルコース低下につながります.
- 繰り返し投与した後の活性,免疫性,または毒性の低下は観察されなかった.
結論:
- IEGは合成ポリマー-バイオポリマー結合物の正確な合成を可能にします.
- 精密調整された合成ポリマー構造は 治療用途の結合性能を最適化するための経路を提供します
関連する概念動画
Insulin: Biosynthesis, Chemistry, and Preparation
490
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...
490
Insulin Formulations: Types and Delivery
258
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...
258
Polymer Classification: Stereospecificity
2.5K
Polymerization generates chiral centers along the entire backbone of a polymer chain. Accordingly, the stereochemistry of the substituent group has a significant effect on polymer properties. Polymers formed from monosubstituted alkene monomers feature chiral carbons at every alternate position in the polymer backbone. Relative to the predominant orientation of substituents at the adjacent chiral carbons, the polymer can exist in three different configurations: isotactic, syndiotactic, and...
2.5K
Protein and Protein Structure
80.4K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
A protein's shape is critical to its function. For example, an enzyme...
80.4K
Glucagon-like Receptor Agonists
389
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
389
Prochirality
3.9K
The concept of prochirality leads to the nomenclature of the individual faces of a molecule and plays a crucial role in the enantioselective reaction. It is a concept where two or more achiral molecules react to produce chiral products. A typical process is the reaction of an achiral ketone to generate a chiral alcohol. Here, the achiral reactant reacts with an achiral reducing agent, sodium borohydride, to generate an equimolar mixture of the chiral enantiomers of the product. For example, an...
3.9K


