Self-Assembly Of Peptide Nucleic Acid (PNA)-Peptide Hybrid Materials And Their Application On Hydrogel Preparation

Peptides and DNA have unique self-assembly properties and superior bio-compatibility,which have attracted more and more attention in the field of nano-biomaterials.Specific short peptide sequences can quickly form fiber structures through self-assembly,and they have been widely used in environmentally responsive biomaterials,nanomedicines and other fields.DNA forms assemblies based on the principle of complementary base pairing,which has stronger designability,and thus can obtain more abundant and diverse nano-morphologies.Hybrid fusion of peptide and DNA self-assembling materials may bring more new properties and assembly strategies,which has a great research significance.Due to the different synthesis methods of DNA and peptides,the construction of DNA-polypeptide complexes also has some challenges,so the research in this area is still very limited.Peptide nucleic acid(PNA),a class of artificially synthesized DNA analogues,has the same base side chains as nucleic acids and the same peptide bond backbone as polypeptides.PNA-polypeptide hybridization sequences can be easily obtained by solid-phase synthesis,which is convenient to study the self-assembly materials of peptide-nucleic acid complex.This thesis explores the design of PNA-polypeptide hybrid self-assembly materials,explores the influence of PNA base sequence on the self-assembly of peptide fibrosis,and hopes to explore a new way of regulating biological self-assembly materials.Based on this,we further constructed a peptide self-assembling hydrogel capable of regulating solution-gel conversion through nucleic acid sequence hybridization.This thesis mainly includes the following three parts:(1)The construction of PNA-peptide system.This section discusses the synthetic circuits of PNA monomers protected by Fmoc / Boc,the principles and processes of PNA and peptide synthesis.The synthesis of a PNA-peptide complex sequences containing guanine(G)are investigated.The polypeptide sequence can form a stable fibrous structure,while the guanine-rich nucleic acid sequence tends to be assembled in the form of nanoparticles.The introduction of such bases with strong self-assembly ability into the polypeptide sequence lay a foundation for studying the effect of PNA bases on the assembly behavior of peptide fibrosis.(2)The effect of G on the regulation of peptide fibrosis structure.This part explores theeffect of pH on the self-assembly morphology of the original polypeptide sequence,and explores the effect of different amounts of G on the structure of the polypeptide assembly,which is confirmed that the connection of GG at the end of the polypeptide can completely inhibit the fibrosis of the polypeptide and form a nano-spherical assembly.The addition of a CC nucleic acid sequence complementary to GG in the solution can inhibit the interaction between GG and make the fibrotic assembly structure of the polypeptide reappear.This study revealed the effect of G base on the fibrosis assembly of peptides for the first time,which provides a new strategy for the design and regulation of peptide self-assembly structures.(3)PNA-polypeptides self-assemble hydrogels.We explored the method for preparing peptide hydrogels using the above peptide-PNA complex sequence.The addition of the CC complementary sequence can quickly induce the PNA-peptide hybridization sequence to form self-assembled fibers,thereby triggering the transformation of the solution into a gel state.The gel can be further functionalized by CC modification.By introducing the CC sequence modified by RGD polypeptide,RGD modified hydrogel can be obtained,which has good biocompatibility,and the gelation process is mild,which does not affect cell viability,which can be used for three-dimensional cell culture.