Conformation and other biophysical properties of cyclic antimicrobial peptides in aqueous solutions
Conformation and other biophysical properties of cyclic antimicrobial peptides in aqueous solutions
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DOI：
10.1034/j.1399-3011.2001.00893.x
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发表时间：
2001-10-01
期刊：
影响因子：
--
通讯作者：
Hodges, RS
中科院分区：
文献类型：
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作者：
Jelokhani-Niaraki, M;Prenner, EJ;Hodges, RS
为了进一步了解环抗菌肽的生物活性机制，在水环境中研究了以gramicidin S （GS）为基础的四种膜活性环肽抗生素的生物物理性质和构象。GS10 [cyclo(VKLdYP)(2)]、GS12 [cyclo(vklkdpkvkldyp)]、GS14 [cyclo(VKLKVdYPLKVKLdYP)]和[d - lys](4)GS14 [cyclo(VKLKVdYPLKVKLdYP)] （d -氨基酸残基用d表示）的环大小分别为10、12和14个残基，具有不同的结构和两致病性，具有广泛的溶血和抗菌活性。GS10、GS12和[D-Lys]4GS14在具有离子强度的生物环境缓冲体系中表现为单体。GS14在低浓度下也是单体，但在bb0 ~ 50ma浓度下聚集。多肽对自组装和与疏水表面相互作用的亲和力与其分子间相互作用的自由能有关。研究了盐、有机溶剂（三氟乙醇）浓度和温度的变化对肽构象的影响。与GS类似，GS10在不同环境和较宽的温度范围内被证明具有稳定且相当刚性的构象，而GS12、GS14和[D-Lys](4)GS14具有更灵活的构象。尽管其构象与GS10相似，但GS14具有独特的物理化学性质，因为它在相对较低的浓度下倾向于聚集。生物物理数据解释了环肽的结构、两亲性和疏水性与其溶血活性之间的直接关系。然而，由于微生物膜结构的多样性，这种与肽抗菌活性的关系具有更复杂的性质。
As a step towards understanding the mechanism of the biological activity of cyclic antimicrobial peptides, the biophysical properties and conformations of four membrane-active cyclic peptide antibiotics, based on gramicidin S (GS), were examined in aqueous environments. These cyclic peptides, GS10 [cyclo(VKLdYP)(2)], GS12 [cyclo(VKLKdYPKVKLdYP)], GS14 [cyclo(VKLKVdYPLKVKLdYP)] and [D-Lys](4)GS14 [cyclo(VKLdKVdYPLKVKLdYP)] (D-amino acid residues are denoted by d and are underlined) had different ring sizes of 10, 12 and 14 residues, were different in structure and amphipathicity, and covered a broad spectrum of hemolytic and antimicrobial activities. GS10, GS12 and [D-Lys]4GS14 were shown to be monomeric in buffer systems with ionic strength biological environments. GS14 was also monomeric at low concentrations, but aggregated at concentrations > 50 mum. The affinity of peptides for self-assembly and interaction with hydrophobic surfaces was related to their free energy of intermolecular interaction. The effects of variations in salt and organic solvent (trifluoroethanol) concentration and temperature on peptide conformation were also examined. Similar to GS, GS10 proved to have a stable and rather rigid conformation in different environments and over a broad range of temperatures, whereas GS12, GS14 and [D-Lys](4)GS14 had more flexible conformations. Despite its conformational similarity to GS10, GS14 had unique physicochemical properties due to its tendency to aggregate at relatively low concentrations. The biophysical data explain the direct relation between structure, amphipathicity and hydrophobicity of the cyclic peptides and their hemolytic activity. However, this relation with the antimicrobial activity of the peptides is of a more complex nature due to the diversity in membrane structures of microorganisms.