以多巴胺为功能单体的生物大分子印迹聚合物

Dopamine-based molecularly imprinted polymers for the recognition of biomacromolecules

分子印迹聚合物(molecularly imprinted polymer, MIP)是指功能单体与模板分子组装后发生聚合,通过移除模板分子得到的聚合物.与天然抗体相比, MIP具有制备简单、成本低廉、稳定性好、可重复使用等优点,因此被广泛地用于分离富集、化学传感、药物运输及生物催化等领域.近年来,分子印迹技术的发展促进了以生物大分子特别是蛋白质为模板的印迹材料的设计、制备和应用研究.由于生物相容性好,聚合反应条件温和且容易调控,多巴胺被用作功能单体在固体基质表面通过自聚合反应印迹生物大分子.本文综述这类分子印迹聚合物的设计和制备方法,并介绍印迹材料的性能表征和应用;重点论述以蛋白质为模板的印迹聚合物,同时兼顾以其他生物大分子如多肽、低聚糖以及病毒、酵母细胞等直接作为模板的印迹聚合物的合成和表征;最后讨论该领域的未来发展趋势和存在的挑战.

Compared to natural antibodies or receptors,molecularly imprinted polymers(MIPs)have shown advantages of easy preparation,low cost,high stability and reusability.MIPs have been widely used in the fields of separation,chemical sensing,drug delivery and biocatalysis.The development of new imprinting methods such as surface imprinting,epitope imprinting,post-imprinting modification have promoted the synthesis and application of MIPs against biomacromolecules.Despite of the success,it remains a challenge to prepare MIPs with high affinity and specificity to the target proteins because the options of water-soluble monomers are very limited and the protein’s conformation is liable to change during the polymerization reaction.The majority of protein imprinting studies employ the five most common monomers:acrylamide(AAm),methacrylic acid(MAA),aminophenylboronic acid(APBA),acrylic acid(AA),and Nisopropylacrylamide(NiPAAm)and the two frequently used crosslinkers,methylenebisacrylamide(MBA)and ethylene glycol dimethacrylate(EGDMA)for preparation of protein imprinted polymers.In recent years,dopamine(DA)has been frequently used for surface modification as it can self-polymerize in alkaline medium at room temperature and generate polydopamine(pDA)films that can adhere onto almost all inorganic and organic surfaces with good biocompatibility.Thus,DA emerged as an appropriate monomer as well as a crosslinker for various imprinting reactions.In this review,we highlighted the recent advances in design and fabrication of DA-based MIPs for various biomacromolecules,including proteins,glycoproteins,bacteria or virus,with focus on protein imprinted polymers.First,we briefly introduced the DA self-polymerization reaction and the reported mechanisms for pDA formation.It is generally accepted that the initial driving force for the formation of pDA is the oxidation of DA to DA-indole by dissolved oxygen in an alkaline solution.Then,we summarized the recent work that employs common protein such as human/bovine serum albumin(HSA/BSA),lysozyme(Lyz),hemoglobin,trypsin and immunoglobulin(IgG)as the imprinting templates.These MIPs were mainly used for separation and purification of the template proteins.We also introduced the combination of protein imprinting with quartz crystal microbalance(QCM),cyclic voltammetry(CV),surface plasmon resonance(SPR)and mass spectroscopy(MS)for recognition and detection of the target proteins.In the following part,we summarized the strategies developed for imprinting of glycoproteins,most of which took advantage of boron affinity reaction or lectin-sugar interaction to improve the affinity and selectivity of the resultant MIPs.Then,we introduced recent work on imprinting of microorganisms such as viruses and bacteria,in which surface imprinting technique and potential analysis or chemiluminescence(ECL)technique are combined to construct biosensors that can selectively detect target species with high sensitivity.In addition,we also introduced the synthesis of a bio-inspired virus imprinted polymer and its application for prevention of viral infections.The techniques which were used for characterizing the properties of the MIP materials,e.g.,adsorption capacity,imprinting factor and selectivity,as well as the proposed theoretical model were also mentioned in the review.Finally,we discussed current challenges and possible solutions for using DA as a monomer to prepare MIPs for biomacromolecules.We believe that the interactions between the intermediate products during dopamine polymerization and the template proteins deserve further investigation,as it may provide more possibilities to modulate the binding properties of the obtained MIPs.