RESUMO
Synthetic calcium transporters are few despite their potential biological significance. Herein, we report small alanine-derived peptides containing pyridyl-triazole motifs for inducing calcium selectivity. The peptides are decorated with hydrophobic alkyl chains to facilitate membrane insertion. The most efficient peptide scaffold has an EC50 value of 0.09 mol % and functions as a calcium carrier.
Assuntos
Cálcio , Peptídeos , Ionóforos , Cálcio/metabolismo , Peptídeos/química , Transporte Biológico , Transporte de ÍonsRESUMO
Synthetic channels with high ion selectivity are attractive drug targets for diseases involving ion dysregulation. Achieving selective transport of divalent ions is highly challenging due their high hydration energies. A small tripeptide amphiphilic scaffold installed with a pybox ligand selectively transports CuII ions across membranes. The peptide forms stable dimeric pores in the membrane and transports ions by a Cu2+ /H+ antiport mechanism. The ligand-induced excellent CuII selectivity as well as high membrane permeability of the peptide is exploited to promote cancer cell death. The peptide's ability to restrict mycobacterial growth serves as seeds to evolve antibacterial strategies centred on selectively modulating ion homeostasis in pathogens. This simple peptide can potentially function as a universal, yet versatile, scaffold wherein the ion selectivity can be precisely controlled by modifying the ligand at the C terminus.
Assuntos
Cobre/metabolismo , Canais Iônicos/antagonistas & inibidores , Mycobacterium/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Oligopeptídeos/farmacologia , Morte Celular/efeitos dos fármacos , Cobre/química , Humanos , Canais Iônicos/metabolismo , Ligantes , Estrutura Molecular , Mycobacterium/crescimento & desenvolvimento , Neoplasias/metabolismo , Neoplasias/patologia , Oligopeptídeos/químicaRESUMO
Synthetic chloride transporters are potential therapeutic agents for cystic fibrosis and cancer. Reported herein are macrocyclic transmembrane chloride transporters prepared by a one-pot condensation reaction. The most efficient macrocycle possesses a fine balance of hydrophobicity for membrane permeation and hydrophilicity for ion recognition. The macrocycle transports chloride ions by forming channels in the membrane. Hydrogen bonds and anion-π interactions assist chloride transport.