Advanced Science (May 2022)
Microbial Metabolite Inspired β‐Peptide Polymers Displaying Potent and Selective Antifungal Activity
- Donghui Zhang,
- Chao Shi,
- Zihao Cong,
- Qi Chen,
- Yufang Bi,
- Junyu Zhang,
- Kaiqian Ma,
- Shiqi Liu,
- Jiawei Gu,
- Minzhang Chen,
- Ziyi Lu,
- Haodong Zhang,
- Jiayang Xie,
- Ximian Xiao,
- Longqiang Liu,
- Weinan Jiang,
- Ning Shao,
- Sheng Chen,
- Min Zhou,
- Xiaoyan Shao,
- Yidong Dai,
- Maoquan Li,
- Lixin Zhang,
- Runhui Liu
Affiliations
- Donghui Zhang
- State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai 200237 China
- Chao Shi
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Zihao Cong
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Qi Chen
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Yufang Bi
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Junyu Zhang
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Kaiqian Ma
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Shiqi Liu
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Jiawei Gu
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Minzhang Chen
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Ziyi Lu
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Haodong Zhang
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Jiayang Xie
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Ximian Xiao
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Longqiang Liu
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Weinan Jiang
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Ning Shao
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Sheng Chen
- Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic Chemistry Research Center for Biomedical Materials of Ministry of Education School of Materials Science and Engineering East China University of Science and Technology Shanghai 200237 China
- Min Zhou
- State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai 200237 China
- Xiaoyan Shao
- Shanghai Ruijin Rehabilitation Hospital Shanghai 200023 China
- Yidong Dai
- Shanghai Ruijin Rehabilitation Hospital Shanghai 200023 China
- Maoquan Li
- Department of Interventional and Vascular Surgery Shanghai Clinical Research Center for Interventional Medicine Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200072 China
- Lixin Zhang
- State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai 200237 China
- Runhui Liu
- State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai 200237 China
- DOI
- https://doi.org/10.1002/advs.202104871
- Journal volume & issue
-
Vol. 9,
no. 14
pp. n/a – n/a
Abstract
Abstract Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL‐diaminopropionic acid) (PDAP) from the ring‐opening polymerization of β‐amino acid N‐thiocarboxyanhydrides, by mimicking ε‐poly‐lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 µg mL−1 against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.
Keywords
- antifungal agents
- fungal keratitis
- host defense peptide mimicking
- poly(DL‐diaminopropionic acid)
- β‐peptide polymers
