Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes.
Nat Chem
; 15(11): 1559-1568, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37814114
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 11 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.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Macrocíclicos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article