Facial amphiphilicity index correlating chemical structures with antimicrobial efficacy

Bioactive Materials

卷:20

JiHyeon Hwang¹  Yuanyuan Luo¹  Rani Kumar¹  Leman Buzoglu Kurnaz¹  Chuanbing Tang¹  Amjed Alabresm²  Ryan Leighton²  Alan W. Decho²  Mitzi Nagarkatti³  Prakash Nagarkatti³  Xiaoming Yang³ 

[1] Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, United States;

[2] Department of Environmental Health Sciences, University of South Carolina, Columbia, SC, 29208, United States;

[3] Department of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia, SC, 29209, United States;

关键词: Antimicrobial;    Facial amphiphilicity;    Chemical structure;    Peptide;   

DOI  :  

来源: DOAJ

【 摘 要 】

Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers. Vast efforts have been dedicated to small molecular, macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation, including local facial amphiphilicity and global amphiphilicity. This work conceptualizes Facial Amphiphilicity Index (FAI) as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy. FAI is a ratio of numbers of charges to rings, representing both compositions of hydrophilicity and hydrophobicity. Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria. Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs. Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid. While low and high FAIs respectively lead to higher and lower antimicrobial efficacy, in consideration of cytotoxicity, the sweet spot is typically suited with intermediate FAIs for each specific system. This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes. The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.

【 授权许可】

Unknown