Identification and Characterisation of the Antimicrobial Peptide, Phylloseptin-PT, from the Skin Secretion of Phyllomedusa tarsius, and Comparison of Activity with Designed, Cationicity-Enhanced Analogues and Diastereomers.
Identification and Characterisation of the Antimicrobial Peptide, Phylloseptin-PT, from the Skin Secretion of Phyllomedusa tarsius, and Comparison of Activity with Designed, Cationicity-Enhanced Analogues and Diastereomers.
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DOI：
10.3390/molecules21121667
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发表时间：
2016-12-03
期刊：
影响因子：
--
通讯作者：
Shaw C
中科院分区：
文献类型：
--
作者：
Gao Y;Wu D;Xi X;Wu Y;Ma C;Zhou M;Wang L;Yang M;Chen T;Shaw C
属于叶隔蛋白家族的抗菌肽主要存在于叶节蛙中。这些肽不仅具有有效的抗微生物活性，而且对真核细胞表现出低毒性。因此，它们被认为是许多疾病的有希望的候选药物。在最近的一项研究中，有效的抗微生物活性与该肽家族成员的保守结构和阳离子两亲性特征相关。在跗叶水母（Phyllomedusa tarsius）的皮肤分泌物中发现了一种phylloseptin肽前体，并通过MS/MS测序验证了成熟肽，随后命名为phylloseptin-PT。化学合成和纯化的phylloseptin-PT显示出对金黄色葡萄球菌和白色念珠菌的活性。然而，一系列阳离子性增强的肽类似物的phylloseptin-PT，其中包含在特定位点的氨基酸取代，表现出显着增加的抗微生物活性相比，天然phylloseptin-PT。此外，替代构象设计和化学合成的d-赖氨酸，表现出强大的抗菌活性和提高生物利用度。这些数据表明，phylloseptin可能是下一代抗生素的潜在候选者。因此，通过修饰天然抗菌肽模板进行合理设计可以为克服其可能的临床应用过程中的障碍提供一条加速途径。
Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a recent study, potent antimicrobial activity was correlated with the conserved structures and cationic amphiphilic characteristics of members of this peptide family. A phylloseptin peptide precursor was discovered here in the skin secretion of Phyllomedusa tarsius and the mature peptide was validated by MS/MS sequencing, and was subsequently named phylloseptin-PT. The chemically-synthesized and purified phylloseptin-PT displayed activity against Staphylococcus aureus and Candida albicans. Nevertheless, a range of cationicity-enhanced peptide analogues of phylloseptin-PT, which contained amino acid substitutions at specific sites, exhibited significant increases in antimicrobial activity compared to native phylloseptin-PT. In addition, alternative conformers which were designed and chemically-synthesized with d-lysine, showed potent antimicrobial activity and enhanced bioavailability. These data indicate that phylloseptins may represent potential candidates for next-generation antibiotics. Thus, rational design through modification of natural antimicrobial peptide templates could provide an accelerated path to overcoming obstacles en-route to their possible clinical applications.
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影响因子：
4.2
作者：
Wan Y;Ma C;Zhou M;Xi X;Li L;Wu D;Wang L;Lin C;Lopez JC;Chen T;Shaw C
通讯作者：
Shaw C
影响因子：
4.8
作者：
Chen, YX;Mant, CT;Hodges, RS
通讯作者：
Hodges, RS
影响因子：
5.8
作者：
Gautier, Romain;Douguet, Dominique;Drin, Guillaume
通讯作者：
Drin, Guillaume
DOI：
10.1016/1056-8719(92)90004-k
发表时间：
1992-12-01
影响因子：
1.9
作者：
TYLER, MJ;STONE, DJM;BOWIE, JH
通讯作者：
BOWIE, JH
DOI：
10.1046/j.1432-1327.1999.00917.x
发表时间：
1999-12-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Suh, JY;Lee, YT;Choi, BS
通讯作者：
Choi, BS