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.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Na H,Li X,Zou C,Wang C,Wang C,Liu Kdoi
10.1016/j.bmc.2016.05.008subject
Has Abstractpub_date
2016-07-01 00:00:00pages
2999-3005issue
13eissn
0968-0896issn
1464-3391pii
S0968-0896(16)30332-7journal_volume
24pub_type
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journal_title：Bioorganic & medicinal chemistry
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