%0 Generic %A Lyu, Yinfeng %A Chen, Tingting %A Shang, Lu %A Yang, Yang %A Li, Zhongyu %A Zhu, Jiang %A Shan, Anshan %D 2019 %T Design of Trp-Rich Dodecapeptides with Broad-Spectrum Antimicrobial Potency and Membrane-Disruptive Mechanism %U https://acs.figshare.com/articles/dataset/Design_of_Trp-Rich_Dodecapeptides_with_Broad-Spectrum_Antimicrobial_Potency_and_Membrane-Disruptive_Mechanism/8953262 %R 10.1021/acs.jmedchem.9b00288.s002 %2 https://acs.figshare.com/ndownloader/files/16370201 %K antimicrobial resistance %K Membrane permeabilization assays %K membrane-disruptive mechanism %K WXYX %K Trp-Rich Dodecapeptides %K H-bond formation sites %K novel antimicrobial agents %K laboratory strains %K peptide design %K antimicrobial activity %K peptide design template %K Antimicrobial peptides %K antibiotic alternatives %K Broad-Spectrum Antimicrobial Potency %K Membrane-Disruptive Mechanism %K α- helical structure %K PMAP -36 %K drug resistance %K antibiotic resistance %K microscope observations %K Trp-rich dodecapeptides %K acid characteristics %X There has recently been great concern regarding antibiotics due to potential drug resistance and the impact of antibiotics on the environment. Antimicrobial peptides are believed to have potential as novel antimicrobial agents to address the problems of antibiotics. Herein, we report a set of Trp-rich dodecapeptides derived from PMAP-36 that are based on the peptide folding principle and the amino acid characteristics. An effective peptide design template, (WXYX)3, where X represents Arg or Lys and Y represents hydrophobic or neutral amino acid, was summarized with the distribution of Trp at H-bond formation sites along the α-helical structure. The template peptide 6 (3W-2), with low amphipathicity, displayed strong antimicrobial activity against laboratory strains and clinical isolates while showing no cytotoxicity. Furthermore, 6 was able to suppress the emergence of antimicrobial resistance. Membrane permeabilization assays and microscope observations revealed the potent membrane-disruptive mechanism of 6. Overall, this study diminishes the randomness in peptide design and provides a strategy for generating effective antibiotic alternatives to overcome antibiotic resistance. %I ACS Publications