Interaction Mechanism Of Cyclodextrins With Hydrophobic Oligopeptides

In recent years,as people’s requirements for drug safety have been continuously improved,highly effective and low-toxic polypeptide drugs have become the focus of attention.However,the instability of polypeptides often affects its widespread use in industrial production.Hydrophobic amino acids are inextricably linked to the physicochemical properties of proteins and peptides.Therefore,we started by studying the interaction between hydrophobic amino acids and cyclodextrins,and further studied the interaction mechanism between hydrophobic oligopeptides and different cyclodextrins.The main research contents and results of this paper are as follows:1)In binding constant experiments,we found that three hydrophobic amino acids had different binding capacity towardβ-cyclodextrin.After preparing and characterizing the inclusion complexes of amino acids andβ-cyclodextrin,it was found that no new chemical bonds were formed during the formation of the inclusion complexes.The supramolecular structure of inclusion complexes was determined by nuclear magnetic resonance(NMR)experiments and molecular docking simulations.The related thermal parameters of the complexes and natural bond orbital(NBO)analysis were calculated to show that the amino acids/β-cyclodextrin complex system with larger binding constants was found to have lower relative interaction energies and more molecular hydrogen bonds in the complex system.2)In this chapter,the dipeptide YW included with different cyclodextrin molecules(M-CD,HPCD,andβ-CD).It was found that the formation of the self-assembly supramolecular system of YW and cyclodextrin did not involve the formation and fragmentation of covalent bonds.Through NMR spectroscopy and molecular docking simulations,the hydroxyl group of tyrosine entered the cavity ofβ-CD.However,the imidazole group of tryptophan entered the cavity when YW combine with HPCD and M-CD.Antioxidant experiments showed that the antioxidant activity of YW/HPCD complex was larger than YW.By calculating the interaction energy in the complex system with the NBO experiment,the results are also consistent with the previous experiments,the order of stability in three system follows:M-CD>HPCD>β-CD.3)Based on the previous experiments,HPCD is used as the host molecule,and three oligopeptides(WY,WYS,WYSL)were used as ligands to form supramolecular complexes.Fluorescence experiments showed that the binding constants of WYS and WY were less than WYSL.Through IR spectroscopy,UV spectroscopy and DSC,it was found that oligopeptides combined to cyclodextrin through non-covalent interactions.According to the change of chemical shift of ~1H-NMR and the molecular docking experiment,the above-mentioned oligopeptide interacts with HPCD through side chain aromatic ring residues to form the complex.The three oligopeptides already had antioxidant activity,but their antioxidant activity had been improved after their formation of complexes with HPCD.By calculating the interaction energy and hydrogen bond energy in the system,it can be found that the energy of the WYSL/HPCD complex was the lowest one,on the contrary,their hydrogen bond energy of the complex was higher than the others.This study provides a reference for the design and application of peptide drugs.