β-多肽聚合物的优化合成及其抗菌活性

Optimum Synthesis and Antimicrobial Activities of Poly-β-peptide Polymers

为了解决不同结构的β-内酰胺单体由于反应活性差异而可能出现的聚合反应不完全的问题,选择了侧链带有疏水性基团、反应速率慢的β-内酰胺单体3,3,4,4-四甲基-2-氮杂环丁酮(TM)和侧链带有正电荷的β-内酰胺单体4-[(叔丁氧羰基氨基)甲基]-3-甲基-2-氮杂环丁酮(MM)制备得到β-多肽聚合物,通过考察反应物浓度、反应溶剂类型、引发剂类型等因素来优化聚合反应。实验结果表明,相对于目前常用的以锂作为反离子的引发剂,以钾作为反离子的引发剂可提高β-多肽聚合物的聚合反应速率和难聚合单体的转化率,增加反应物浓度和优化溶剂体系均可改善聚合反应速率。通过测定优化条件下所得聚合物的最小抑菌浓度(ρMIC),观察到聚合物对某些微生物的抗菌活性有所提高。

In order to address the incomplete polymerization of different monomers resulted by their different reactivities,we perform a polymerization of β-lactam monomer bearing hydrophobic sidechains,3,3,4,4-tetramethylazetidine-2-one(TM)and another monomer having positively charged groups in the sidechain,3-(tert-butyloxycarbonyl aminomethyl)-4,4-dimethylazetidin-2-one(MM),which show slow reactivity during polymerization.The polymerization condition of these monomers was optimized by exploring different monomer concentrations,reaction solvents and initiators.The results indicated that initiators with potassium counter ion can initiate a faster polymerization of β-lactam monomers and result in a higher conversion of monomers compared with that with lithium counter ion.In addition,increasing the reactant concentration and optimizing the reaction solvent could also increase the reaction rate.The investigations on the minimum inhibitory concentration(ρMIC)of synthesized polymers revealed that the polymers obtained at the optimized reaction conditions presented slightly increased antimicrobial activities against some types of microbes.