The lipidation and glycosylation enabling bioactivity enhancement and structural change of antibacterial peptide G3

Ruipin Cao; Li Li; Zuxian Xu; Jiaxin Li; Danli Wu; Yinglu Wang; Hu Zhu

doi:10.1016/j.bmcl.2023.129322

The lipidation and glycosylation enabling bioactivity enhancement and structural change of antibacterial peptide G3

Bioorg Med Chem Lett. 2023 Jun 15:90:129322. doi: 10.1016/j.bmcl.2023.129322. Epub 2023 May 13.

Authors

Ruipin Cao¹, Li Li¹, Zuxian Xu¹, Jiaxin Li¹, Danli Wu¹, Yinglu Wang², Hu Zhu³

Affiliations

¹ Fujian-Taiwan Science and Technology Cooperation Base of Biomedical Materials and Tissue Engineering, Engineering Research Center of Industrial Biocatalysis, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, Fujian 350007, China.
² Fujian-Taiwan Science and Technology Cooperation Base of Biomedical Materials and Tissue Engineering, Engineering Research Center of Industrial Biocatalysis, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, Fujian 350007, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China. Electronic address: wangyl@fjnu.edu.cn.
³ Fujian-Taiwan Science and Technology Cooperation Base of Biomedical Materials and Tissue Engineering, Engineering Research Center of Industrial Biocatalysis, Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, Fujian 350007, China. Electronic address: zhuhu@fjnu.edu.cn.

PMID: 37182609
DOI: 10.1016/j.bmcl.2023.129322

Abstract

Bacterial resistance has led to increased interest in the use of antibacterial peptides (AMPs), but their clinical application is limited by poor stability and solubility, as well as complex cytotoxicity. Chemical modification is a common strategy to modulate AMPs. In this study, a de novo designed AMP (G3) was modified by adding an alkyl acid at the N-terminal and a monosaccharide at the C-terminal. Bio-activity assays demonstrated that conjugation with n-caprylic acid increased the peptide's antibacterial activity and permeabilized the membrane. Attachment of glucose or galactose at the C-terminal improved its biofilm inhibitory capacity and marginally reduced cytotoxicity. The hybrid peptide, containing both n-caprylic acid and galactose, exhibited excellent antibacterial and antibiofilm activity, as well as permeabilized the outer membrane.

Keywords: Antibacterial peptides; Biofilm; Glycosylation; Lipidation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Antimicrobial Cationic Peptides* / chemistry
Galactose*
Glycosylation
Microbial Sensitivity Tests

Substances

octanoic acid
Antimicrobial Cationic Peptides
Galactose
Anti-Bacterial Agents