Metal Ions Modulating Self-assembly Of Short Peptide Conjugating Nonsteroidal Anti-inflammatory Drugs(NSAIDs)

Metal ions are essential components that help maintain the processes of normal life,and they can be used to fabricate self-assembled building blocks for peptide derivatives,proteins and nucleic acids.Self-assembly behavior of natural proteins is closely related to many life activities and disease processes.In order to have a deep understanding of the assembly proceeding of peptide drugs and the abnormal assembly behavior of diseaserelated proteins,assembled dipeptide-derivative-conjugated drug molecules were taken as the research objective,and the microstructure,mechanical strength and shape recovery property of supramolecular hydrogels include by metal ions were studied.In addition,the possible assembly mechanism was proposed and the reason of its shape memory performance was explored.The main contents are as follows:First,assembled dipeptide-derivative-conjugated drug molecules have attracted extensive attention due to its good retention,small side-effects and strong permeability.Here,a novel strategy to construct supramolecular hydrogels modulated using metal cations was developed via standard solid-phase peptide synthesis(SPPS).Upon introducing a variety of metal ions into aqueous solutions of a gelator(naproxen-FF),including a nonsteroidal anti-inflammatory drug(NSAID)and dipeptide,stable hydrogels was obtained.It is found that these hydrogels exhibit excellent mechanical properties and thixotropy,as well as superb responsivity to multiple metal ions.Due to the significance of potassium ions in biological processes,the K-triggered hydrogel has been chosen as a model,and its self-assembly mechanism has been explored via various spectral analysis processes.In addition,the self-assembly performances of peptides are significantly affected by the chemical structures of the gelator molecules.This work provides deep insight into the aggregation mechanism of dipeptide-derivative-conjugated drug molecules through introducing a variety of metal ions,laying the foundation for further biological applications.Second,the hydrogel was obtained after optimizing the gelation conditions,including chemical structure of gelator,solubilizer,the type and dosage of metal ions and the form of salt solution.It was found that the hydrogel exhibits excellent both selfhealing and shape recovery properties.Specifically,the hydrogel shows sharp and reversible “sol-gel” phase transition response to temperature and external force.The material properties of the Na-triggered hydrogel recovered when transitioning from high strain to low strain,displaying the injectable and self-healing properties of the Natriggered hydrogel by the step-strain test.Given this condition,a series of experiments were designed to explain the self-assembly mechanism reasonably.As confirmed by spectroscopic characterization,the noncovalent interactions are involved in the selfassembly process,such as hydrogen bonding,?-? stacking and Na+-? interactions.