Design,Synthesis And Antifreeze Property Study Of α-Peptoid Oligomers

Ice formation can cause great damage in most cases.For example,ice crystals formed during the low temperature process will cause mechanical damage to the cells,which greatly affects the effect of cryopreservation of tissues and cells,and inhibits the development of biomedical engineering.Therefore,how to control the formation and growth of ice crystals is of great importance.Antifreeze proteins（AFPs）are good antifreeze agents,but their applications are greatly limited by their cytotoxicity,low stability and high cost,besides their TH activity is not desirable in cryopreservation.Thus,cheap biocompatible antifreeze agents with IRI but no TH activities are highly desirable.Peptoids are important peptidomimetic polymers that are easy to synthesize and much more resistance to enzymatic degradation than peptides,making them potential candidate as antifreeze agent in application as preservation of food and organ.However,only a few efforts have explored the effect of peptoids as antifreeze agent and their IRI activity has not been reported.In this work,we report the first ice recrystallization inhibition（IRI）activity study of peptoids and their structure-property relationships.A series of protein mimetic peptoid hexamers with side chains bearing typical hydrophobic groups（-CH₃ and-CH₂CH₃）and hydrophilic groups（-OH,-COOH,-NH₂）were successfully designed and synthesized through solid-phase submonomer synthesis method.IRI study indicates that all peptoids exhibit no TH but IRI effects,i.e.slowing down ice crystal growth and decreasing ice crystal grain size,Peptoid with hydroxyethyl substituents on side chains shows the best IRI activity,Mean largest grain size（MLGS）is 50.34mm decreased by 73%compared with the negative control PBS buffer(MLGS_PBS=187.58mm),suggesting the strong hydrogen bond between the side chain of the peptoids and the ice crystal is an important factor for the inhibition of recrystallization.Ice morphology study indicates that in the presence of peptoids with methyl,ethyl and aminoethyl side chains,a representatively hexagonally shaped ice crystal was observed with further growth over time after a disc-shaped single ice crystal was held for a few minutes.However,for the peptoid with hydroxyethyl or carboxyethyl substituent,the morphology remains a typical flat disc-shaped crystal,just like pure water.Which suggests the matching degree of the spatial configuration of the side chain structure of the peptoids and the crystal lattice of ice crystals is a key factor for ice morphology modulation.In a word,after nearly 30 years of development,peptoids as a new biomimetic material to replace polypeptide have made rapid progress in synthesis methods and performance study that expands its application in chemical catalysis,biomedicine,nanomaterials and other fields.We believe this study will facilitate the development of synthetic antifreeze agents that can mimic the structure and function of AFPs in cryopreservation application.