Rational Design Of Asp-Phe Based Hbonding Networks And Their Application In Smart Materials

With an in-depth understanding of life science,massive extraordinary artificial biomaterials have been explored and applied in biomedicine field.However,the complexity of physiology and diversity of biomolecules become obstacles in designing the biomaterials with high sensitivity and specificity.Inspired by nature,one emerging topic in artificial biomaterial field is the construction of smart materials in combination of oligopeptide blocks capable of recognizing the targets in the complex vitro/vivo environment.It should be noted that the structure and function of peptide could be varied by the diverse species,different linkages and specific locations of amino acids.Therefore,these oligopeptide-based materials if can be designed in a controllable and tunable way,could be endowed with higher accuracy and specificity,facilitating the development of smart materials in cancer early diagnose,tumor cell separation,drug-release systems,separation and purification,bio-imaging and bio-sensors,etc.In this study,the research on the dipeptide-based smart materials are divided into two main parts.The first part presents a biomimetic design for sialylated glycan-specific smart polymer,and the second part illustrates the species and conformation of amino acid residues on the effect of gelation and modulation of gel-sol response rate.Detailed discussion and results are demonstrated below.1.Directed by the previous dipeptide screening strategy,an L-Asp-L-Phe?DF?with the combination of a hydrophobic and a hydrophilic amino acid residue has been introduced as an optimized saccharide receptor.The dipeptide was prepared by a standard solid-supported peptide synthesis process.The hydrogen nuclear magnetic resonance titration?¹H NMR?experiment indicated that this dipeptide had strong and differential binding affinity with Neu5Ac,Gal,GlcNAc,Man or Glc?core fragments of the sialo-complex type glycans?.Then L-Asp-L-Phe was grafted onto a branched polyethyleneimine?PEI?main chain?average molecular weight of 10,000?with a grafting ratio of approximately 6%for construction of a N-sialylated glycan targeted biomimetic polymer.And this L-Asp-L-Phe grafted polyethyleneimine?PEI-g-DF?polymeric thin film displays remarkable adsorption ability toward model sialylated glycans,even can discriminate their linkage isomers,accompanied with significant changes in surface morphology and stiffness.A molecular mechanism was further explored for explaining the intermolecular complexation between PEI-g-DF and sialo-complex-type N-linked glycans.The commercially 3'-sialylactose sodium salt was chosen to represent the characteristic sialylated glycan fragment.The isothermal titration microcalorimetry?ITC?measurement,¹H NMR titration and Bio-ATR-FTIR experiments indicated that carbonyl,amide and hydroxyl groups in 3'-sialyllactose and dipeptide carbonyl groups in the polymer participated in the complexation between PEI-g-DF and saccharides.And PEI was presumed to play more important role in constructing favorable polymeric conformation promoting the dipeptide better in combination with the glycan.Furthermore,these features facilitate highly selective capture of sialylated glycopeptides from complex protein sample by functional prorous magnetic silicate microspheres,PEI-g-DF@mSiO₂@SiO₂@Fe₃O₄.Excellent glycan-discrimination,strong adsorption capacities,high specific surface area and magnetic characteristic of our material contributed to its excellent performance in glycopeptide capture.A high proportion of sialo-complex-type glycopeptides has been identified via magetic-solid-phase extraction strategy from tryptic digests of fetuin mixed with as high as 200-fold bovine serum albumin interference,which validated our glycan-target designing concept.2.The second part focuses on the self-assembly behavior of oligopeptide-based micromolecules consisting of a photo-responsive azo-benzene and two dipeptide arms.The species and location of amino acid residues on the effect of gelation and modulation of gel-sol response rate have been sysmatically discussed.A peptide consists of multiple amino acids with a specific sequence,and the location and chirality of amino acids strongly affects the orientations of their chains,the folding of the peptide backbone,and even the bio-function of peptide.In this respect,eight pairs of photo-responsive chiral molecules have been prepared for exploring the role of amino acid residues in the behaviors of smart dipeptide-based gels.The gelation ability and photo-responsiveness,as well as the gel-sol transition speed and self-assemled morphology before and after UV radiation at low or high concentration have been systematically investigated.A competitive mechanism was proposed for this chiral effect,the peptide sequence,the introduction of?-?stacking interaction,amino acid species and chiral conformation would have great effect on the photo-induced isomerization and the gelation,namely the disassembly and self-assembly behaviors of molecules.The results validate the peptide sequence,amino acid location and chiral conformation would have great effect on the competition balance between E/Z isomerization and gelation of photo-responsive dipeptide-based molecules.