Antimicrobial activity and stability of protonectin with D-amino acid substitutions.

Shuai Qiu, Ranran Zhu, Yanyan Zhao, Xiaoping An, Fengjing Jia, Jinxiu Peng, Zelin Ma, Yuanyuan Zhu, Jiayi Wang, Jinhuan Su, Qingjun Wang, Hailin Wang, Yuan Li, Kairong Wang, Wenjin Yan, Rui Wang

Journal of peptide science : an official publication of the European Peptide Society 2017 May

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The misuse and overuse of antibiotics result in the emergence of resistant bacteria and fungi, which make an urgent need of the new antimicrobial agents. Nowadays, antimicrobial peptides have attracted great attention of researchers. However, the low physiological stability in biological system limits the application of naturally occurring antimicrobial peptides as novel therapeutics. In the present study, we synthesized derivatives of protonectin by substituting all the amino acid residues or the cationic lysine residue with the corresponding D-amino acids. Both the D-enantiomer of protonectin (D-prt) and D-Lys-protonectin (D-Lys-prt) exhibited strong antimicrobial activity against bacteria and fungi. Moreover, D-prt showed strong stability against trypsin, chymotrypsin and the human serum, while D-Lys-prt only showed strong stability against trypsin. Circular dichroism analysis revealed that D-Lys-prt still kept typical α-helical structure in the membrane mimicking environment, while D-prt showed left hand α-helical structure. In addition, propidium iodide uptake assay and bacteria and fungi killing experiments indicated that all D-amino acid substitution or partially D-amino acid substitution analogs could disrupt the integrity of membrane and lead the cell death. In summary, these findings suggested that D-prt and D-Lys-prt might be promising candidate antibiotic agents for therapeutic application against resistant bacteria and fungi infection. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Citation

Shuai Qiu, Ranran Zhu, Yanyan Zhao, Xiaoping An, Fengjing Jia, Jinxiu Peng, Zelin Ma, Yuanyuan Zhu, Jiayi Wang, Jinhuan Su, Qingjun Wang, Hailin Wang, Yuan Li, Kairong Wang, Wenjin Yan, Rui Wang. Antimicrobial activity and stability of protonectin with D-amino acid substitutions. Journal of peptide science : an official publication of the European Peptide Society. 2017 May;23(5):392-402