Construction Of Artificial Ion Channnels Based On Macrocycle-peptide Backbone

In the living body,natural channel proteins are macromolecular pores embedded in the cell membrane.It can mediate the transport of various polar nutrients in the hydrophobic region of the cell membrane and play a key role in the process of material exchange and metabolism in living cells.However,due to its complex structure and easy inactivation,any abnormalities in the human body can cause a series of channel diseases.In order to study the transmembrane transport mechanism of natural channel proteins,scientists have designed and synthesized a variety of powerful artificial transmembrane transport systems based on peptides or macrocyclic compounds.Although great progress has been made in this field,constructing artificial ion channels with good selectivity and high transport efficiency is still a research hotspot.In this thesis,we combined macrocyclic compounds with peptides and designed a series of single-molecule artificial transmembrane channels based on the macrocyclic-polypeptide backbone,which mainly includes the following two parts:In the first part of the work,based on the pillararene-gramicidin backbone,we used the click reaction to connect the dialkynyl pillar[5]arene with the azido-containing peptide molecule;synthesized neutral,positively and negatively charged single tubular molecules by electric charge and its electrostatic control.Through the fluorescence experiment and the single-channel current experiment,it was found that the target molecules exhibited a good ability to incorporate into lipid membranes,and realized transmembrane transport by the"channel"mechanism.At the same time,we found that the negatively charged channel molecules showed the best potassium ion transport efficiency and highest K~+/Cl~-selectivity.Experiments have shown that electrostatic interactions have an important effect on the transmembrane transport activity of channel molecules.In the second part of the work,based on the cyclodextrin-short peptide skeleton,we extracted an effective potassium ion filter TVGYG peptide sequence from natural potassium channel proteins,and then introduced tryptophan and glycine to increase the peptide sequence length.Finally,we used the click sequence to link the peptide sequence withα-cyclodextrin through a covalent bond to synthesize a series of single-molecule artificial transmembrane ion channels with potassium ion selectivity.