期刊
CHEMMEDCHEM
卷 13, 期 19, 页码 2030-2036出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201800525
关键词
galectin-3; molecular recognition; NMR spectroscopy; tumor-associated carbohydrate antigens; X-ray crystallography
资金
- Fundacao para a Ciencia e Tecnologia (FCT) Portugal [UID/Multi/04378/2013]
- FEDER [POCI-01-0145-FEDER-007728]
- FEDER through COMPETE 2020
- POCI
- PORL
- FCT through PIDDAC
- FCT [IF/00780/2015, PTDC/BBB-BEP/0869/2014]
- COST Action [CM1407]
- iNEXT - Horizon 2020 programme of the European Union [653706, MX16609]
- [022161]
- [FCT-ANR/BBB-MET/0023/2012]
Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90% of adenocarcinomas. Additionally, the binding of the TF antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction have the potential to prevent cancer metastasis. A multidisciplinary approach combining the optimized synthesis of a TF antigen mimetic with NMR, X-ray crystallography methods, and isothermal titration calorimetry assays was used to unravel the molecular structural details that govern the Gal-3/TF mimetic interaction. The TF mimetic has a binding affinity for Gal-3 similar to that of the TF natural antigen and retains the binding epitope and bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective, a decrease in the enthalpic contribution was observed for the Gal-3/TF mimetic complex; however, this behavior is compensated by a favorable gain in entropy. From a structural perspective, these results establish our TF mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and for likely use in hampering Gal-3-mediated cancer cell adhesion and metastasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据