Reducing Self-Assembly by Increasing Net Charge: Effect on Biological Activity of Mastoparan C
Hai Bui Thi Phuong, Binh Le Huy, Khanh Nguyen Van, Ngan Dang Thi, Thuong Bui Thi, Yen Nguyen Thi Hai, Tung Thanh Bui, Huy Luong Xuan, Binh Nguyen Thi Thanh
Abstract
The ability of amphipathic peptides to arrange themselves in aqueous solutions, known as self-assembly, has been found to reduce the effectiveness of these peptides in interacting with cell membranes. Therefore, minimizing their tendency to self-assemble could be a potential strategy for enhancing the pharmacological properties of antimicrobial peptides (AMPs). To explore this idea, this study prepared a series of natural peptides mastoparan C ( MPC ) with increased net charge and hydrophilicity via alanine-to-lysine substitution and investigated the impact on the biological activity. The preliminary data suggested the influence of both the overall positive charge and the position of a lysine residue on the self-assembly of MPC and its derivatives. Besides, the analogue MPC-A5K,A8K displayed higher anticancer activity and comparable antimicrobial activity with significantly lower hemolysis than MPC . Hence, reducing self-assembly by expanding the cationic area could be a promising approach for developing potent and selective AMPs.