Alpha-beta chimeric polypeptide molecular brushes display potent activity against superbugs-methicillin resistant Staphylococcus aureus

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  • ReceivedAug 17, 2018
  • AcceptedSep 5, 2018
  • PublishedSep 21, 2018


Funded by

This research was supported by the National Natural Science Foundation of China(21574038,21774031)

the National Natural Science Foundation of China for Innovative Research Groups(51621002)

the National Key Research and Development Program of China(2016YFC1100401)

the Natural Science Foundation of Shanghai(18ZR1410300)

the “Eastern Scholar Professorship” from Shanghai local government(TP2014034)

the national special fund for State Key Laboratory of Bioreactor Engineering(2060204)

the 1000 Talent Young Scholar program in China

111 project(B14018)

and the program for professor of special appointment at ECUST.


This research was supported by the National Natural Science Foundation of China (21574038 and 21774031), the National Natural Science Foundation of China for Innovative Research Groups (51621002), the National Key Research and Development Program of China (2016YFC1100401), the Natural Science Foundation of Shanghai (18ZR1410300), the “Eastern Scholar Professorship” from Shanghai local government (TP2014034), the national special fund for State Key Laboratory of Bioreactor Engineering (2060204), the 1000 Talent Young Scholar program in China, 111 project (B14018), and the program for professor of special appointment at ECUST. The authors thank Research Center of Analysis and Test of East China University of Science and Technology for the help on the characterization. We also thank Prof. Hua Lv and Prof. Lichen Yin for valuable discussions on NCA synthesis and purification.

Interest statement

The authors declare that they have no conflict of interest.

Contributions statement

Liu R designed and directed the project; Zhang D, Ma P synthesized the samples; Zhang D, Zhang Q and Qiao Z did the characterization of samples; Zhang D, Zhang S, Shao N, Qian Y, Xie J, Dai C, Qi F, Zhang W and Cheng S and Zhou R performed the biological experiments; Liu R, Zhang D analyzed the data; Liu R, Zhang D and Zhang S wrote the paper. All authors reviewed the manuscript.

Author information

Danfeng Zhang was born in 1992. He received his BSc degree majored in material science and engineering from East China University of Science and Technology (ECUST) in 2018. His research interest is polymeric antimicrobial material.

Runhui Liu obtained BSc in pharmaceutical engineering in 2001 at East China University of Science & Technology. He obtained PhD in Organic Chemistry 2009 at Purdue University. Afterward, he worked as a postdoc at California Institute of Technology and University of Wisconsin-Madison. In 2014, he took a professor position in the School of Materials Science and Engineering at ECUST. His current research focuses on polypeptide polymers for antimicrobial and tissue engineering applications.


Supplementary information

Experimental details and supporting data are available in the online version of the paper.


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  • Figure 1

    Synthesis of α/β CPMBs. (a) Synthetic route of α/β CPMBs; (b) sideview of α/β CPMBs carton; (c) 3D view of the α/β CPMBs carton; (d) GPC traces of PβAA backbone and α/β CPMB at the amine protected stage.

  • Figure 2

    Cytotoxicity of α/β CPMBs toward (a) HUVEC (ATCC PCS-100-010), (b) NIH 3T3 fibroblast cells (ATCC CRL-1658), (c) HaCaT (BNCC342026) and (d) MDCK (NBL-2, ATCC CCL-34). The concentrations of PβAA-g-PαLL10 and PβAA-g-PαLL20 used for cytotoxicity experiments are related to their MIC value against S. aureus USA300 as shown in Table 2. The value of MIC is 0.38 µmol L−1 for PβAA-g-PαLL10 and 0.26 µmol L−1 for PβAA-g-PαLL20

  • Figure 3

    SEM characterization of MRSA cell morphology change after bacteria incubation with the α/β CPMB. (a) MRSA cells without antimicrobial treatment as control and (b) MRSA cells incubated with α/β CPMB for 20 min.

  • Table 1   NMR and GPC characterizations of α/β CPMBs



    GPC characterizationa


    Mn (kDa)























    GPC characterization on polypeptide at the amine protected stage using DMF as the mobile phase at a flow rate of 1 mL min−1.

  • Table 2   Antibacterial activity of α/β CPMBs against multiple strains of MRSA

    Antimicrobial compound

    MIC (MBC)a µmol L−1


    USA300 Lac





    0.38 (0.38)

    0.38 (0.38)

    0.38 (0.38)

    0.38 (0.38)

    0.38 (0.38)


    0.26 (0.26)

    0.26 (0.26)

    0.26 (0.26)

    0.26 (0.26)

    0.26 (0.26)








    0.26 (0.52)

    0.52 (0.52)

    0.52 (0.52)

    0.26 (0.52)

    0.26 (0.52)

    Magainin II






    MIC (minimum inhibitory concentration) is the minimum compound concentration to inhibit bacteria growth; MBC (minimum bactericidal concentration) is the minimum compound concentration to kill bacteria; b) ND means activity is not detected even under the highest compound concentration at 77.8 µmol L−1.


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