色素向基因组使用由糖基工程酵母衍生出的曼诺-6-酸盐甘氨酸
Seobin Kim1,2, Jiyeon Kang1, Danbi An1
1Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea.
Bioconjugate chemistry
|March 1, 2025
概括
lysosome-targeting chimeras (LYTACs) 现在使用酵母衍生的甘氨酸来实现更简单,更安全的蛋白质降解. 这种新的LYTAC配方通过向PD-L1.1来增强癌细胞的杀死.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- lysosome-targeting chimeras (LYTACs) 通过细胞 lysosomes 降解蛋白质.
- 之前的LYTACs依赖于复杂的,潜在的免疫性合成糖.
- 挑战包括聚M6Pn.的合成复杂性和免疫性风险.
研究的目的:
- 开发一种新的LYTAC配方,使用酵母衍生的甘氨酸来改善 lysosomal 运输.
- 为了克服LYTAC构建中合成糖的局限性.
- 评估新型LYTAC在降解PD-L1和增强抗癌免疫力的有效性.
主要方法:
- 经过糖基工程的酵母衍生mannose-6-phosphate glycans (gyM6pGs) 被制造和修改.
- 使用无铜点击化学,将gyM6pGs与抗PD-L1纳米体结合,从而产生LYTACgyM6pG.
- 在体外评估LYTACgyM6pG降解PD-L1和增强T细胞细胞毒性的能力.
主要成果:
- LYTACgyM6pG通过M6PR通路成功向并降解内源性和重组性PD-L1.
- 新型LYTAC配方显示T细胞介导的细胞毒性对癌细胞增强.
- 酵母衍生的gyM6pGs被证明是合成糖的可行和可扩展的替代品.
结论:
- LYTACgyM6pG为LYTAC开发提供了一种简化和更安全的方法.
- 这项技术在推进癌症治疗方面具有重大潜力.
- 使用糖基工程酵母甘氨酸为可扩展的LYTAC生产铺平了道路.
相关概念视频
Oligosaccharide Assembly
2.8K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.8K
Lysosomal Hydrolases
3.7K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.7K
Export of Misfolded Proteins out of the ER
3.4K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.4K
Protein Glycosylation
6.7K
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...
6.7K
Delivery Pathways to the Lysosome
6.1K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.1K


