Triterpene sapogenin-polyarginine conjugates exhibit promising antibacterial activity against Gram-positive strains

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• 作者：Heiya Na ; Xiangpeng Li ; Cunbin Zou ; Chenhong Wang ; Chao Wang ; ^{chaow301@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Keliang Liu ; ^{keliangliu55@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Triterpene sapogenin ; Polyarginine peptide ; Antibacterial activity ; Click chemistry ; Synergistic effect
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：24
• 期：13
• 页码：2999-3005
• 全文大小：909 K

文摘

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.