title: Triterpene sapogenin-polyarginine conjugates exhibit promising antibacterial activity against Gram-positive strains.
abstract: Triterpene sapogenins are a group of biologically active compounds with antibacterial activity. However, the limited solubility and poor bioavailability of triterpene sapogenins restrict their therapeutic application. Polyarginine peptides are small cationic peptides with high affinities for multiple negatively charged cell membranes and possess moderate antibacterial activities. In this study, we designed and synthesized a series of sapogenin-polyarginine conjugates in which the triterpene sapogenin moiety was covalently appended to the positively charged polyarginine via click chemistry. A clear synergistic effect was found, and the conjugates exhibited potent and selective antibacterial activity against Gram-positive strains. Among them, BAc-R3 was the most promising compound, which was also proven to be nontoxic toward mammalian cells as well as stable in plasma. The mechanism of BAc-R3 primarily involves an interaction with the bacterial membrane, similar to that of antimicrobial peptides (AMPs). This scaffold design opens an avenue for the further development of novel antibiotics comprised of the combination of a peptide and a natural product.
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Heiya
authors.initials: H
authors.lastname: Na
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Xiangpeng
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Cunbin
authors.initials: C
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Chenhong
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China. Electronic address: chaow301@gmail.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China. Electronic address: keliangliu55@126.com.
authors.forename: Keliang
authors.initials: K
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D010949:Plasma / Q000737:chemistry; D012502:Sapogenins / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D012502:Sapogenins; D014315:Triterpenes; C015462:polyarginine
keywords: Antibacterial activity; Click chemistry; Polyarginine peptide; Synergistic effect; Triterpene sapogenin