Influence of Proline Substitution on the Bioactivity of Mammalian-Derived Antimicrobial Peptide NK-2
Influence of Proline Substitution on the Bioactivity of Mammalian-Derived Antimicrobial Peptide NK-2
复制标题
脯氨酸取代对哺乳动物源抗菌肽NK-2生物活性的影响
DOI：
10.1007/s12602-017-9335-1
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发表时间：
2018-03
影响因子：
4.9
通讯作者：
赵丽
中科院分区：
文献类型：
--
作者：
闫洁熙;梁晓磊;赵丽
多重耐药细菌正在成为全球威胁，因此迫切需要寻找替代化合物。抗菌肽（AMP）因其独特的作用机制以及作为传统抗生素的替代或补充的可能性而成为一个有前途的热点。然而，更好地了解抗菌肽结构与其生物活性之间的关系对于开发下一代抗菌药物至关重要。 NK-2源自哺乳动物蛋白NK-lysin，具有有效的抗肿瘤和杀菌能力。由于脯氨酸因其构象受限而被认为是有效的α螺旋破坏者，为了更好地理解脯氨酸在NK-2构效关系中的作用，我们构建了两个NK-2类似物。我们检查了 NK-2 及其脯氨酸取代类似物的生物活性，并分析了由此产生的构象变化。我们的结果表明，将脯氨酸引入NK-2的一级序列中，通过改变α-螺旋含量，显着降低了抗肿瘤、抗菌和细胞毒性作用以及DNA结合活性。然而，α-螺旋含量并不是唯一的决定因素，脯氨酸插入的位置也很关键。这项研究将有助于更清楚地了解脯氨酸在 NK-2 结构和生物活性中的作用，并为未来的研究奠定基础。
Multidrug-resistant bacteria are emerging as a global threat, making the search for alternative compounds urgent. Antimicrobial peptides (AMPs) became a promising hotspot due to their distinct action mechanism and possibility to be used as an alternative or complement to traditional antibiotics. However, gaining a better understanding about the relationship between antimicrobial peptides structure and its bioactivity is crucial for the development of next generation of antimicrobial agents. NK-2, derived from mammalian protein NK-lysin, has potent antitumor and bactericidal abilities. As proline was considered to be an effective α-helix breaker due to its restricted conformation, to better comprehend the effects of proline in the structure-activity relationship of NK-2, we constructed two NK-2 analogs. We examined the biological activities of NK-2 and its proline substitution analogs and analyzed the resulting conformational changes. Our results showed that introducing proline into the primary sequence of NK-2 significantly decreased the antitumor, antibacterial, and cytotoxic effects, as well as DNA binding activity by changing the α-helix content. However, α-helical content was not the only determining factor, the position of proline inserted was also critical. This study will allow for clearer insight into the role of proline in structure and bioactivity of NK-2 and provide a foundation for future studies.
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影响因子：
1.8
作者：
Andersson, M;Gunne, H;Gudmundsson, GH
通讯作者：
Gudmundsson, GH
影响因子：
--
作者：
C. Rohl;R. L. Baldwin
通讯作者：
C. Rohl;R. L. Baldwin
影响因子：
3.5
作者：
Biondi, Barbara;Casciaro, Bruno;Mangoni, Maria Luisa
通讯作者：
Mangoni, Maria Luisa
影响因子：
3.9
作者：
Jie-xi Yan;Kairong Wang;Ru Chen;Jingjing Song;Bang-zhi Zhang;W. Dang;Wei Zhang;Rui Wang
通讯作者：
Jie-xi Yan;Kairong Wang;Ru Chen;Jingjing Song;Bang-zhi Zhang;W. Dang;Wei Zhang;Rui Wang
DOI：
10.1073/pnas.58.1.52
发表时间：
1967-07
影响因子：
11.1
作者：
P. Schimmel;P. Flory
通讯作者：
P. Schimmel;P. Flory