Construction Of Heteromonodisperse Polyethylene Glycol Derivatives Based On Ion Exchange And Solid Phase Synthesis Strategy

The difficulty of cancer treatment is mainly due to the lack of selective delivery of anticancer drugs to tumor tissues.Conventional anticancer drugs have poor selectivity for tumor cells,leading to non-therapeutic systemic side effects while they are being treated.At present,chemical modification technology has been widely studied and applied in many fields,such as biomedicine,food,chemical engineering,health,etc.,and has become an important means to improve the biological and clinical performance of biomolecules.In recent years,chemical modifiers are widely favored by researchers in the chemical industry.However,polyethylene glycol and its derivatives are one of the more commonly used chemical modifiers in chemical modification technology.In the research and application of polyethylene glycol and its derivatives,researchers have found that the end groups of polyethylene glycol play a decisive role in widening its application range and applicability.Characteristics,play different roles,and have more advantages in practical applications,the application prospects are more extensive.Based on the many advantages of isomerized polyethylene glycol,this project first uses dihydroxy polyethylene glycol with a number average molecular weight of 600 as the starting material,and designs an experimental route.The end group is modified to synthesize one end with a number average molecular weight of 600 Heterobifunctional polyethylene glycol with a carboxyl group at one end of the hydroxyl group was separated and purified by DEAE Sephadex A-25 dextran gel resin.It was found by mass spectrometry that although such a heterobifunctional polyethylene glycol has expanded the application range of polyethylene glycol,there are still problems such as molecular weight heterogeneity,low reaction yield,many side reactions,and incomplete reactions.(The isolated yield of DEAE Sephadex A-25 is about 33.33%,and the separation ratio of the three compounds OH-PEG600-COOH / HOOCPEG600-COOH / OH-PEG600-OH is about 2.5: 2.5: 5).In order to further solve these problems of traditional PEG,through reading a large number of literatures,we further designed a heterogeneous monodisperse polyethylene glycol derivative with a single component,structure and molecular weight.First,tetraethylene glycol was selected as the starting material,and monodispersed heterobifunctional octaethylene glycol derivatives were synthesized by optimizing the reaction conditions in several steps.In order to further increase the molecular weight of the monodisperse PEG,we then connected the carboxyl group of the octaethylene glycol derivative to the polymer solid phase carrier by a covalent bond through solid-phase synthesis,followed by the amino terminal of the octaethylene glycol derivative as below A starting point of synthesis,after removing the protective group at the amino terminal,a condensation reaction is performed with the carboxyl terminal of excess glutamic acid activation,and then the amino terminal of this glutamic acid is used as the next starting point of synthesis,and Excessive octaethylene glycol derivativeactivated carboxyl groups undergo a condensation reaction to extend the PEG chain.Finally,the target PEG derivative is cleaved from the resin,and after separation and purification,the desired monodisperse polyethylene glycol derivative 2000(amino acid alternating polyethylene glycol with a different molecular weight and a space stretch structure)is obtained,AAPEGs).The whole synthesis process explored the synthesis,post-treatment and purification of target compounds in detail.The target compound was analyzed for molecular structure and molecular weight by NMR and mass spectrometry.This subject has carefully optimized the entire synthesis process.The results show that the glutamic acid-containing alternating monodisperse heterofunctional diethylene glycol derivative 2000 was successfully synthesized with a purity of 99%.This synthesis method not only solves the problem of non-uniformity due to traditional polyethylene glycol A series of problems caused by sex have also expanded the application range of polyethylene glycol derivatives.It is hoped that the new compounds synthesized in this subject can provide directions for the development of new drugs in the future.