Effects of linker amino acids on the potency and selectivity of dimeric antimicrobial peptides

Stapled Wasp Venom-Derived Oncolytic Peptides with Side Chains Induce Rapid Membrane Lysis and Prolonged Immune Responses in Melanoma

“…Cationic NCPs exhibit strong oncolytic activity by lysing cancer cell membranes, a mechanism of action with a decreased tendency to induce resistance. − Along with the structural characterization of NCPs, certain NCPs and their derivates are the focus of drug development as novel antitumor agents. − As the shortest (10-amino acids), amphipathic, linear α-helical NCP from the venom sac of the spider wasp, Anoplius samariensis, anoplin has attracted much attention on the account of its simple structure, broad spectrum of activities, and lack of hemolytic toxicity . However, further development of the linear form of anoplin has been hindered by its conformational instability, susceptibility to proteolytic degradation, and suboptimal therapeutic activity. − All-hydrocarbon stapling has been considered one of the most promising strategies for constraining peptides in an α-helical conformation to form protein epitope mimetics with improved bioactivity and increased proteolytic stability. − However, all-hydrocarbon stapling has never been applied to oncolytic NCP design. The tumor membrane lytic capacity of anoplin exhibits high dependency on its α-helical structure, , making anoplin an ideal template for modification by peptide stapling.…”

Development of Neuropeptide Hemokinin-1 Analogues with Antimicrobial and Wound-Healing Activity

“…subtilis as AH-3 (Table ). Previous studies by our group and others have reported that a kink in the helical structure conferred by the introduction of proline can increase the killing activity of AMPs against bacterial cells by facilitating their membrane disturbance and membrane pore formation. ,− As shown in Table , further disrupting the helical structure by substituting proline for glycine did not affect the potency of AH-5 against E. coli and B.…”

“…Like glycine, proline is also a well-known helix breaker. However, the introduction of proline around the center position of helical AMPs with long sequences can remarkably improve their antimicrobial activity and reduce hemolytic activity. − Therefore, in this study, AH-5 was designed by substituting proline for glycine at position 10 of AH-3. The sequences and structural parameters of hHK-1 and its analogues are shown in Table .…”

Advances in the Study of Structural Modification and Biological Activities of Anoplin

“…To break α-helix and obtain greater flexibility of heterodimeric AMPs, Kai et al ( 2018 ) used different amino acids ( 7–9 , Figure 2C ), including Leu, Pro, and Ahx (aminocaproic acid), as linker to connect anoplin and mastoparan, another α-helical AMP from Vespula lewisii venom. Findings manifested that Pro and Ahx contributed to the design of ideal dimer AMPs with high selectivity and potency while reducing lytic activity with respect to red blood cells.…”

“…As a wasp venom peptide, anoplin ( 1 , Figure 1 ) was isolated from the venom sac of the Japanese solitary spider wasp Anoplius samariensis (Hisada et al, 2000 ). Anoplin is the shortest, amphipathic, linear α-helical antimicrobial peptide (AMP) with only 10 residues (Gly-Leu-Leu-Lys-Arg-Ile-Lys-Thr-Leu-Leu-NH 2 ) (Konno et al, 2001 ; Jittikoon, 2015 ); it also exhibits a wide range of biological activities including antibacterial (Konno et al, 2001 ; Monincová et al, 2010 ), mast cell degranulating (Cabrera et al, 2009 ), antitumor (Zhu et al, 2013 ; Da Silva et al, 2018 ; Kai et al, 2018 ), antimalarial (Carter et al, 2013 ), antifungal (Jindrichova et al, 2014 ), and anti-inflammatory activities (Zhong et al, 2020b ). Anoplin exerts its functions by direct interaction with anionic bilayers and biological membranes via ion channels (Cabrera et al, 2008 ; Leung et al, 2011 ), selectively binding to the bacterial DNA or inhibiting ATP synthase (Syed et al, 2018 ).…”