Synthetic histatin analogues with broad-spectrum antimicrobial activity
Synthetic histatin analogues with broad-spectrum antimicrobial activity
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DOI：
10.1042/bj3260039
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发表时间：
1997-08-15
影响因子：
4.1
通讯作者：
Amerongen, AVN
中科院分区：
文献类型：
--
作者：
Helmerhorst, EJ;VantHof, W;Amerongen, AVN
组胺素是唾液中富含组氨酸的阳离子肽，长度范围为7至38个氨基酸残基，其在体外对白色念珠菌发挥有效的杀伤作用。从组胺素5的C-末端杀真菌结构域（残基11-24，称为dh-5）开始，化学合成了许多取代类似物，以研究螺旋构象的肽的两亲性对杀念珠菌活性的影响。在dh-5的几个位置上的单取代对杀真菌活性没有任何影响。然而，多位点取代的类似物（dhvar 1和dhvar 2）表现出比dh-5高6倍的活性。此外，dhvar 1和dhvar 2抑制了临床分离株中发现的第二种最常见的酵母菌（光滑球拟酵母菌）、口腔和非口腔病原体（如中间普雷沃氏菌和变形链球菌）以及耐甲氧西林金黄色葡萄球菌的生长。在其广谱活性方面，dhvar 1和dhvar 2与两栖动物来源的抗菌肽爪蟾抗菌肽（PGLa和爪蟾抗菌肽2）相当。dhvar 1、dhvar 2和爪蟾抗菌肽的杀真菌和溶血活性均随离子强度的降低而增加。
Histatins are salivary histidine-rich cationic peptides, ranging from 7 to 38 amino acid residues in length, that exert a potent killing effect in vitro on Candida albicans. Starting from the C-terminal fungicidal domain of histatin 5 (residues 11-24, called dh-5) a number of substitution analogues were chemically synthesized to study the effect of amphipathicity of the peptide in helix conformation on candidacidal activity. Single substitutions in dh-5 at several positions did not have any effect on fungicidal activity. However, multi-site substituted analogues (dhvar1 and dhvar2) exhibited a 6-fold increased activity over dh-5. In addition, dhvar1 and dhvar2 inhibited the growth of the second most common yeast found in clinical isolates, Torulopsis glabinta, of oral-and non-oral pathogens such as Prevotella intermedia and Streptococcus mutans, and of a methicillin-resistant Staphylococcus aureus. In their broad-spectrum activity, dhvar1 and dhvar2 were comparable to magainins (PGLa and magainin 2), antimicrobial peptides of amphibian origin, Both the fungicidal and the haemolytic activities of dhvar1, dhvar2 and magainins increased at decreasing ionic strength.