Chiral Mechanism Of Deoxynucleosides-Short Peptides Co-assembly

The discovery and development of natural amyloid materials with strong self-assembly capabilities have contributed to the unique position of peptides in the field of nano-biomimetic supramolecules.Over the years,peptides have proven to be excellent structural units for creating more complex supramolecular structures and functions.Compared with other structural units,peptides have many unique biotechnological application characteristics,such as biocompatibility,sequence-specific secondary structure,chemical diversity,ease of biomolecular recognition and synthesis,etc.These characteristics can promote their use in Biological materials and medical fields have considerable potential value.Nucleic Acid,peptides,and carbohydrate have been extensively studied in systems that mimic biological chiral assembly.As an important non-chiral component,bases are usually covalently bound to sugar rings and play an important role in the formation of the DNA double helix structure.However,it is not clear how non-chiral bases play a role in chiral self-assembly in the presence of chiral sugar ring modifications.Here,we investigate self-co-assembly based on chiral amino acids and chiral nuclear bases to understand the role of chiral molecules in multiple dissociable assemblies.In this paper,D/L-deoxynucleoside（D/L-d A,D/L-d T）was synthesized by chemical synthesis method,and was co-assembled with short peptide I₃E and I₃^DE with C-terminal of glutamate.According to CD and FTIR,with the addition of deoxynucleoside,the secondary structure of the assembly changed from random coil toβ-sheet,and the assembly shape showed that the addition of deoxynucleoside could change the helix direction of the I₃^DE short peptide assembly from left-handed to right-handed helix.Compared with the D-d T system,the helical direction change of the I₃^DE system with L-d T is more obvious,indicating that the chirality of deoxynucleoside plays a crucial role in the process of co-assembly.With the prolongation of the assembly time,the assembly fibers will develop from single fiber to aggregated fiber bundles,and finally the fiber bundles will aggregate and fuse to form large nanorods.At the same time,due to the difference of p Ka between deoxynucleoside and peptides,deoxynucleoside and peptides have the same or different charge when p H is in a certain range,and the effect of electrostatic interaction in the process of production is stronger than weak interaction such as hydrogen bond.In order to explore the influence of electrostatic interaction in the assembly process,I₃H series of short peptides were designed.Due to the weak hydrogen bond interaction between histidine and deoxynucleoside,there was basically no significant influence on the assembly results.In contrast,we use the imidazole group of histidine side chain to regulate the charge of deoxynucleoside and short peptide molecules by adjusting the environmental p H in a certain range of response to environmental p H.When p H=7.0,a large number of fine fibers are entangled among the assembly fibers of the co-assembly system,and the length of the fibers added with D-d A becomes shorter.However,when p H=3.0,the length of self-assembled fibers was almost the same as that of the short peptide,and there was no fiber entanglement.This indicates that electrostatic interaction has a great influence on the weak hydrogen bond co-assembly system and the co-assembly of short peptide and deoxynucleoside is a result of the joint influence of multiple forces.