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.
Viral infection has become one of the worst human lethal diseases. In recent years, major gains have been made in the research of peptide-based antiviral agents on account of the mechanism of viral membrane fusion, among which the peptide Enfuvirtide has been listed for the treatment of AIDS. This paper reviewed a new way to design peptide-based antiviral agents by "bundling" superhelix with isopeptide bonds to construct the active advanced structure. It can solve the problem that peptide precursor compounds derived from the natural sequence of viral envelope protein tend to aggregate and precipitate under physiological conditions and low activity and endow the peptide agents with the feature of thermal stability, protease stability and in vitro metabolic stability. This approach is also providing a new way of thinking for the research and development of broad-spectrum peptide-based antiviral agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.