Fu Tsung-Hao, Li Yan, Thaker Hitesh D, Scott Richard W, Tew Gregory N
Polymer Science and Engineering Department, University of Massachusetts , 120 Governors Drive, Amherst, Massachusetts 01003, United States.
PolyMedix, Inc. , 170 North Radnor-Chester Road, Suite 300, Radnor, Pennsylvania 19087, United States.
ACS Med Chem Lett. 2013 Jul 22;4(9):841-5. doi: 10.1021/ml400155a. eCollection 2013 Sep 12.
A novel series of synthetic mimics of antimicrobial peptides (SMAMPs) containing triazole linkers were assembled using click chemistry. While only moderately active in buffer alone, an increase in antimicrobial activity against Staphylococcus aureus and Escherichia coli was observed when these SMAMPs were administered in the presence of mouse serum. One compound had minimum inhibitory concentrations (MICs) of 0.39 μg/mL and 6.25 μg/mL, respectively, and an HC50 of 693 μg/mL. These values compared favorably to peptide-based antimicrobials. A correlation between the net positive charge and SMAMP antimicrobial activity was observed. The triazole linker, an amide surrogate, was found to provide better antimicrobial activity against both S. aureus and E. coli when compared to other analogues.
利用点击化学合成了一系列含三唑连接子的新型抗菌肽模拟物（SMAMPs）。这些SMAMPs单独在缓冲液中时活性一般，但在小鼠血清存在的情况下给药时，对金黄色葡萄球菌和大肠杆菌的抗菌活性增强。一种化合物对金黄色葡萄球菌和大肠杆菌的最低抑菌浓度（MICs）分别为0.39μg/mL和6.25μg/mL，半数溶血浓度（HC50）为693μg/mL。与基于肽的抗菌剂相比，这些数值表现良好。观察到净正电荷与SMAMP抗菌活性之间存在相关性。与其他类似物相比，发现作为酰胺替代物的三唑连接子对金黄色葡萄球菌和大肠杆菌均具有更好的抗菌活性。
