2023-10-09 バッファロー大学(UB)
◆研究者は合成分子を使用してイオンを細胞膜を通じて運び、粘液除去に必要な液体層を50%増加させました。この研究は、システィック・ファイブローシスの治療法を開発する可能性を示唆しています。
<関連情報>
- https://www.buffalo.edu/news/releases/2023/10/ion-ferry-cystic-fibrosis.html
- https://www.nature.com/articles/s41557-023-01315-w
芳香族ペンタアミド大環状化合物が生体膜を通過する陰イオンと高い親和性で結合することを発見 Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes
Ruikai Cao, Robert B. Rossdeutcher, Yulong Zhong, Yi Shen, Daniel P. Miller, Thomas A. Sobiech, Xiangxiang Wu, Laura Sánchez Buitrago, Karishma Ramcharan, Mark I. Gutay, Miriam Frankenthal Figueira, Pia Luthra, Eva Zurek, Thomas Szyperski, Brian Button, Zhifeng Shao & Bing Gon
Nature Chemistry Published:DOI:https://doi.org/10.1038/s41557-023-01315-w
Abstract
The convergent positioning of functional groups in biomacromolecules leads to good binding, catalytic and transport capabilities. Synthetic frameworks capable of convergently locking functional groups with minimized conformational uncertainty—leading to similar properties—are highly desirable but rare. Here we report C5-symmetric aromatic pentaamide macrocycles synthesized in one pot from the corresponding monomers. Their crystal structures reveal a star-shaped, fully constrained backbone that causes ten alternating NH/CH hydrogen-bond donors and five large amide dipoles to orient towards the centre of the macrocycle. With a highly electropositive cavity in a high-energy unbound state, the macrocycles bind anions in a 1:1 stoichiometry in solution, with high affinity for halides and very high affinity for oxoanions. We demonstrate that such macrocycles are able to transport anions across lipid bilayers with a high chloride selectivity and restore the depleted airway surface liquid of cystic fibrosis airway cell cultures.
