Design And Self-assembly Of DNA-peptide Conjugates

As naturally occurring polymers,DNAs and peptides have become research hotspots in the fields of self-assembly and nanotechnology in recent years.However,most used only one type of building block such as DNAs or peptides for self-assembly in the current self-assembly field,which limits the diversity of structure and function of nanomaterial.Although nanotechnology has made great progress,the self-assembly modules are far less complicated than the life activity in a single cell existing in nature.Nature shows the biodiversity with simple structures and exquisite designs.Obviously,the spontaneous functional self-assembly devices in nature are the best examples for self-assembly design in vitro.Inspired by the natural self-assembly examples such as nucleoproteins,viruses,nucleosomes and so on,which self-assembled from nucleic acids and proteins,a series of nanomaterial with different morphologies were obtained by self-assembly of DNA-peptide conjugates in this paper.The controllable constructions of the DNA-peptide nanocomposite system not only enable the effective combination of two basic self-assembly modes in biology to provide an more complicated biological structure template,but also contribute to the in-depth understanding of the interaction of biological macromolecules in vivo.These experimental results may have a certain impact on biomimetic devices manufacturing and biomedical applications.1.DNA-collagen like peptide(DNA-CLP)conjugates self-assembled into nanostructures with different morphologies under different conditions.(1)DNA-CLP conjugates were synthesized by Cu~+catalyzed azide-alkynyl cycloaddition(CuAAC)click chemistry.The reaction was carried out using tris(3-hydroxypropyltriazolylmethyl)amine(THPTA)as Cu~+ligand in a neutral pH PB buffer with high yield,and the reaction product was purified by 15%urea-denatured polyacrylamide gel electrophoresis(PAGE).(2)Two kinds of the trimer formed DNA-CLP conjugates self-assembled at 4°C to form nanoparticles with a diameter of approximately 25 nm.Moreover,the self-assembly behavior of the nanoparticles were closely related to the concentration of the conjugates.(3)Two kinds of annealed DNA-CLP conjugates self-assembled into nanowires up to several microns in length with a width of approximately22 nm and a height of approximately 9 nm.Further transmission electron microscope(TEM)characterization showed that the formation of the nanowires is extremely related to the self-assembly time.2.DNA nanotubes containing the DNA-TTR14 conjugates co-assembled with the amyloid peptide TTR14 to form hybrid nanomaterial.(1)Based on small circular DNA,DNA nanotubes with different self-assembly strategies were designed.Atomic force microscopy(AFM)characterization showed that DNA nanotubes self-assembled with high efficiency,uniform size and dispersion.The measured diameter was consistent with the theoretical value of the design.(2)Then,the amyloid peptide TTR14 was synthesized by Fmoc solid-phase synthesis,and TTR14 self-assembled into amyloid fibers with a width of 15 nm and a height of 4 nm.The self-assembly results showed that the modification at the both ends of amyloid peptide TTR105-115 did not affect its ability to assemble into amyloid fibers.(3)The DNA-TTR14 conjugates was also synthesized by the click reaction,and the DNA nanotubes containing the conjugates co-assembled with the amyloid peptide TTR14 to form hybrid nanomaterial comprising both DNA nanotubes and amyloid fibers.