関連する実験動画
Updated: May 25, 2026

11:21
Bioinformatics Resources for the Study of Glycan-Mediated Protein Interactions
Published on: January 20, 2022
ヒトのアシアログリコプロテイン受容体のグリコミメティックリガンド
Sreeman K Mamidyala1, Sanjay Dutta, Boris A Chrunyk
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|January 28, 2012
まとめ
研究者らは,アシアログリコプロテイン受容体 (ASGPR) との結合親和性を著しく強化する新しいガラクトシール類似体を開発した. これらの改良されたリガンドは,治療薬の標的型肝臓投与に有望である.
科学分野:
- バイオケミストリー バイオケミストリー
- 薬物の配達 薬物の配達
- 肝臓病理学 肝臓病理学
背景:
- アシアログリコプロテイン受容体 (ASGPR) は,銀河糖を含むリガンド結合に不可欠な肝細胞が発現する受容体である.
- ネイティブASGPR基板は低結合親和性を示し,効果的な肝臓配送のためにより強力なリガンドを必要とします.
研究 の 目的:
- ASGPR.への親和性が強化された新しいガラクトシールアナログを合成し,評価する.
- 改善されたリガンド設計のために,ギャラクソシル部分の様々な位置での修正を調査する.
主な方法:
- アノメール,C2,C5,C6の位置での置換による多様なガラクソシル類の合成.
- ASGPR.の合成アナログの結合親和性の評価
主要な成果:
- トリフローロメチラセタミドのいくつかの誘導体は,結合親和性が有意に増加したことを示した.
- 新しいリガンドは,N-アセチルガラクトサミンと同等またはそれ以上の親和性を達成した.
- C3,C4-ダイオルの両側の修正はよく許容され,浅い結合ポケットモデルと一致しました.
結論:
- ギャラクソシルピラノースモチーフは,強化されたASGPRターゲティングのための機能化に適しています.
- 開発されたリガンドは,低マイクロモラーまたはより高い親和性を提供し,治療用のペイロード結合に適しています.
- これらの発見は,高度な肝臓薬剤投与システムへの道を開く.
関連する概念動画
Glucagon-like Receptor Agonists
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 the...
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 the...
Oral Hypoglycemic Agents: Glinides
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively manages...
Protein Glycosylation
Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
Glycosylation occurs in...
GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are typically...
Acarbose and miglitol are typically...
Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...

