- 作者: Sheng-Hung Wang, Tsai-Jung Wu, Chien-Wei Lee and John Yu
- 作者服務機構: 1.Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, and Chang Gung University, Taoyuan, 333, Taiwan 2.Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
The use of in silico strategies to develop the structural basis for a rational optimization of glycan-protein interactions remains a great challenge. This problem derives, in part, from the lack of technologies to quantitatively and qualitatively assess the complex assembling between a glycan and the targeted protein molecule. Since there is an unmet need for developing new sugar-targeted therapeutics, many investigators are searching for technology platforms to elucidate various types of molecular interactions within glycan-protein complexes and aid in the development of glycan-targeted therapies. Here we discuss three important technology platforms commonly used in the assessment of the complex assembly of glycosylated biomolecules, such as glycoproteins or glycosphingolipids: Biacore analysis, molecular docking, and molecular dynamics simulations. We will also discuss the structural investigation of glycosylated biomolecules, including conformational changes of glycans and their impact on molecular interactions within the glycan-protein complex. For glycoproteins, secreted protein acidic and rich in cysteine (SPARC), which is associated with various lung disorders, such as chronic obstructive pulmonary disease (COPD) and lung cancer, will be taken as an example showing that the core fucosylation of N-glycan in SPARC regulates protein-binding affinity with extracellular matrix collagen. For glycosphingolipids (GSLs), Globo H ceramide, an important tumor-associated GSL which is being actively investigated as a target for new cancer immunotherapies, will be used to demonstrate how glycan structure plays a significant role in enhancing angiogenesis in tumor microenvironments. - 中文關鍵字:
- 英文關鍵字: Glycan, Glycosphingolipid, Conformational changes, SPARC, Globo H Ceramide, Molecular modeling, Biacore, Molecular docking, Molecular dynamics