Natural Drug Discovery Group, School of Pharmacy, Queen's University Belfast, Belfast, Northern Ireland, UK.
AG Systematik und Evolutionsbiologie, IBU-Faculty V, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.
Int J Biol Sci. 2018 Apr 25;14(6):599-607. doi: 10.7150/ijbs.23419. eCollection 2018.
Mastoparan is a typical cationic and amphipathic tetradecapeptide found in wasp venom and exhibits potent biological activities. Yet, compared with other insect-derived peptides, such as melittin from the bee venom, this family have been underrated. Herein, we evaluated the biological activities of mastoparan-C (MP-C), which was identified from the venom of the European Hornet (), and rationally designed two analogues (a skeleton-based cyclization by two cysteine residues and an N-terminal extension via tat-linked) for enhancing the stability of the biological activity and membrane permeability, respectively. Three peptides possessed broadly efficacious inhibiting capacities towards common pathogens, resistant strains, as well as microbial biofilm. Although, cyclized MP-C showed longer half-life time than the parent peptide, the lower potency of antimicrobial activity and higher degree of haemolysis were observed. The tat-linked MP-C exhibited more potent anticancer activity than the parent peptide, but it also loses the specificity. The study revealed that MP-C is good candidate for developing antimicrobial agents and the targeted-design could improve the stability and transmembrane delivery, but more investigation would be needed to adjust the side effects brought from the design.
蜂毒素是一种典型的阳离子和两亲性十四肽，存在于黄蜂毒液中，具有很强的生物学活性。然而，与其他昆虫来源的肽，如来自蜜蜂毒液的蜂毒素相比，该家族的研究一直被低估。本文中，我们评估了 Mastoparan-C（MP-C）的生物学活性，该肽是从欧洲大黄蜂（）毒液中鉴定出来的，并通过两个半胱氨酸残基的骨架环化和通过 tat 连接的 N 端延伸分别设计了两种类似物，以提高其稳定性和膜通透性。三种肽对常见病原体、耐药株和微生物生物膜均具有广泛的抑制作用。虽然环化的 MP-C 的半衰期比母肽长，但观察到其抗菌活性的效力降低和溶血程度升高。tat 连接的 MP-C 表现出比母肽更强的抗癌活性，但它也失去了特异性。该研究表明，MP-C 是开发抗菌药物的良好候选物，靶向设计可以提高稳定性和跨膜传递，但需要进一步研究来调整设计带来的副作用。
