Preparation And Properties Of Thermo-sensitive Proline-based Polypeptides

Thermo-sensitive polymer is a kind of intelligent material that can make a reversible response to the outside temperature change.In recent years,thermo-sensitive polymers have been used in many areas such as drug release,bio-separation,and enzyme immobilization.For thermo-sensitive polymers,the most important parameters are the lower or upper critical solution temperatures(LCST and UCST),and biodegradability and biocompatibility.Good biodegradability and biocompatibility provide the basis for its application in the biomedicine.In this paper,the amino acids were used as raw material to synthesize their corresponding amino acid N-carboxyanhydride monomers,and then thermo-sensitive polypeptides with good biocompatibility were prepared.The paper is divided into four parts:First,in the literature review section,the advance of thermo-sensitive polymers was briefly introduced including the outline of the peptide,classification and practical application.Second,the amino acid N-carboxyanhydride(NCA)monomer was prepared from natural amino acid L-proline and sarcosine as raw materials,and the thermosensitive polymer poly(L-proline-co-sarcosine)(PPS)and systematically characterized by FTIR,1H NMR,UV and CD.Unlike ordinary thermosensitive polymers,PPS has a lower critical temperature(LCST = 37?)and a higher critical temperature(UCST = 30?)in the process of heating,and the PPS aqueous solution is in the process of heating and cooling,Showing complex multiphase transformation behavior,such as "?".The results of the CD study show that the introduction of sarcosine in the molecular chain of the polymer in the process of temperature rise and cooling effectively changes the original secondary structure,resulting in the transition from one configuration to another,resulting in the emergence of PPS.The first phase transition,with the temperature continues to rise H bond interaction decreased or disappeared,PPS appeared a second phase change.In addition,the survival rate of HeLa cells in PPS solution was found to be about 70% after 24 h and 48 h,indicatingexcellent biocompatibility.In conclusion,this new polypeptide,PPS,with thermo-sensitivity and low cytotoxicity,has a promising prospect in biomedicine.Third,amino acid N-carboxyanhydride(NCA)monomers were prepared from natural amino acid L-proline and L-alanine as raw materials,and then poly(L-proline-co-L-alanine)(PPA)was systematically characterized by 1H NMR,FTIR,UV and CD.According to the PPA aqueous solution with the temperature curve shows that the temperature rise LCST = 75?,cooling LCST = 42?.From the CD diagram can be seen at different temperatures,the curve changes in the form of almost the same,is a typical random coil structure,which proved that the secondary structure of the material did not change,PPA secondary structure has a strong heat stability.In addition,in the PPA solution,after 24 h and 48 h,HeLa cell survival rate is still about 90%,indicating that PPA no significant cytotoxicity.In general,temperature-responsive polypeptides have significantly contributed to the development of next-generation biomaterials,especially biomedical and pharmaceutical materials.Fourth,amino acid N-carboxyanhydrides(NCA)were prepared by ring closing reaction of L-phenylalanine and L-proline with triphosgene,and the ring opening polymerizations about two NCAs were then conducted to get a polypeptide with thermo-sensitivity and biocompatibility.The results indicated that when the ratio of L-phenylalanine N-carboxyanhydride to L-proline N-carboxyanhydride was controlled at 1:4,poly(L-proline-co-L-phenylalanine)(PPPh)showed thermo-sensitivity.The lower critical solution temperature(LCST)is 71?,and the obvious hysteresis exists during the heating and cooling run.At the same time,the survival rate of HeLa cells was over 100% in the PPPh peptide aqueous solution after 24 h,48 h and 72 h cultivation,indicating that PPPh polypeptide has excellent biocompatibility.In summary,PPPh,as a thermo-sensitive peptide,can be applied in the biomedical fields such as drug release and biological separation.