Study On Synthesis,Conformation And Self-assembly Properties Of Special Short Peptides Containing Dehydroamino Acids

Self-assembled nanostructures are used as drug delivery systems to improve the bioavailability and stability of drugs.Peptide-based nanostructures have attracted much attention due to their excellent biocompatibility.By taking advantage of the intrinsic properties of amino acids,synthetic peptides can be easily transformed into a variety of functional self-assembled nanostructures.Dehydropeptides（DDPs）containing dehydroamino acids（DDAAs）,also known as unsaturated amino acids,are characterized primarily by a carbon-carbon double bond that is often located between C^αand C^β.Intermolecular forces and molecular conformations are important factors affecting molecular self-assembly.In this study,dehydropeptide(DDP 1,Boc-（Z）C^α,β-?Phe-Gly-NHMe)was prepared;its conformation was confirmed to be more stable than the original peptide Boc-DL-Phe（β-OH）-Gly-NHMe（2）by nuclear magnetic resonance（NMR）and X-ray crystal diffraction experiments.Stable molecular conformation and intermolecular forces are very important for molecular self-assembly.DDP monomers were self-assembled to form dehydropeptide nanomaterials（DDPNs）,which were studied by Fourier transform infrared（FTIR）spectroscopy,scanning electron micrography（SEM）,and transmission electron microscopy（TEM）experiments.FTIR results showed that hydrogen bonding is the main driving force of self-assembly.Electron microscope images displayed that the slender DDPN nanofibers formed a dense network.Observations of cell activity and enzyme hydrolysis proved that DDPN has excellent biocompatibility and resistance to the enzymatic hydrolysis of protease K.The antitumor drug temozolomide（TMZ）was loaded on the DDPN with a very high percent entrapment efficiency（EE）of 83.72±4.30%（n=8）and percent drug loading efficiency（LE）of 6.70±0.34%（n=8）.Incubated at physiological p H for 1.5 h,the release of TMZ on DDPN was over 84.92%,and the half-life of TMZ-loaded DDPN was 2.5–3 times longer than that of pristine TMZ.The mechanism of DDPN loading and protecting TMZ was studied.The in vitro cell viability results revealed that compared with pristine TMZ,TMZ-loaded DDPN exhibited higher antitumor activity against U118-MG.The uptake of U118-MG cells incubated with TMZ-loaded DDPN was higher than that of pristine TMZ.Studies of DDPN will provide inspiration for the design of biocompatible nanocarriers resistant to enzymatic hydrolysis in drug delivery systems.