2019年10月5日
Remodeling of the Oligosaccharide Conformational Space in the Prebound State To Improve Lectin-Binding Affinity.
Biochemistry
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- 巻
- in press
- 号
- 34
- 開始ページ
- 3180
- 終了ページ
- 3185
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/acs.biochem.9b00594
We developed an approach to improve the lectin-binding affinity of an oligosaccharide by remodeling its conformational space in the precomplexed state. To develop this approach, we used a Lewis X-containing oligosaccharide interacting with RSL as a model system. Using an experimentally validated molecular dynamics simulation, we designed a Lewis X analogue with an increased population of conformational species that were originally very minor but exclusively accessible to the target lectin without steric hindrance by modifying the nonreducing terminal galactose, which does not directly contact the lectin in the complex. This Lewis X mimetic showed 17 times higher affinity for the lectin than the native counterpart. Our approach, complementing the lectin-bound-state optimizations, offers an alternative strategy to create high-affinity oligosaccharides by increasing populations of on-pathway metastable conformers.
- リンク情報
- ID情報
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- DOI : 10.1021/acs.biochem.9b00594
- PubMed ID : 31553574