Design,Synthesis And Property Study Of Side Chain Oligoethylene Glycol-Modified Fluorinated Peptidic Biomaterials

Polyethylene glycols（PEGs）are used widely in biomedicine,which are commonly used to modify various small molecule drugs and biological macromolecules,and have many excellent properties,such as:improving solubility,extending half-life,reducing side effects,reducing immunogenicity and so on.So PEGylation is one of the common drug modification strategies.In addition,PEGs are also increasingly used in drug delivery systems.Although PEGs are widely used,the heterogeneity of PEGs is an issue.In order to address this issue,our group proposed a method for synthesizing monodisperse PEGs（M-PEGs）based on the ring-opening of cyclic sulfate,and through the solid phase peptide synthesis（SPPS）,a method of synthesizing large molecular weight M-PEGs was explored.Based on these strategies,a series of linear or highly branched oligoethylene glycol-modified peptidic biomaterials were synthesized,we also explored physicochemical and biological properties of these M-PEGs modified peptidic biomaterials,found the M-PEGs size,peptidic biomaterials size and geometry,have a significant effect on these properties.Based on these,a series of side chain oligoethylene glycol-modified fluorinated peptidic biomaterials were synthesized by methoxy-functionalized M-PEGs amino acid derivatives and fluorine-containing lysine derivatives.Through various evaluations,we found them not only have high biocompatibility,improved thermostability and plasma stability,but also can be used for fluorine-19 magnetic resonance imaging(¹⁹F MRI),drug delivery and so on.By comparing linear,side chain and highly branched oligoethylene glycol-modified peptidic biomaterials,we found the lower critical solution temperature（LCST）of linear oligoethylene glycol-modified peptidic biomaterials is lower,side chain and highly branched oligoethylene glycol-modified peptidic biomaterials have higher biocompatibility.These conclusions can provide some ideas for subsequent flexibly designing,quantitatively fine-tuning and predicting the properties of these M-PEGs modified peptidic biomaterials.