Salivary histatin 5: dependence of sequence, chain length, and helical conformation for candidacidal activity.
Salivary histatin 5: dependence of sequence, chain length, and helical conformation for candidacidal activity.
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DOI：
10.1016/s0021-9258(19)39678-4
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发表时间：
1990-03
期刊：
影响因子：
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通讯作者：
P. A. Raj;M. Edgerton;Michael J. Levine
中科院分区：
文献类型：
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作者：
P. A. Raj;M. Edgerton;Michael J. Levine
组胺素5（Asp 1-Ser-His-Ala 4-Lys-Arg-His-His 8-Gly-Tyr-Lys-Arg 12-Lys-Ph e-His-Glu 16-Lys-His -His-Ser 20-His-Arg-Gly-Tyr 24），存在于人腮腺唾液中的碱性富组氨酸肽之一及其几个片段，1-16（N16）、9-24（C16）、11-24（C14）、13-24（C12），15-24（C10）和7-16（M10）通过固相程序合成。还纯化了来自人腮腺唾液的天然组胺素5。它们对两株白色念珠菌的抗真菌活性进行了研究，并通过圆二色性研究了它们在水溶液和非水溶液中的构象偏好。合成的histatin 5、C16和C14肽具有很高的活性，并抑制C.白色念珠菌合成的组胺素5的杀念珠菌活性数据与从腮腺唾液中分离的天然组胺素5的值和先前报道的值相当，尽管所使用的测定系统和所检查的菌株不同。C16片段与整个肽本身一样具有活性，而N16片段的活性远低于C14，表明C-末端的序列对其杀真菌活性很重要。C-末端序列的链长从12个残基增加到16个残基增加了杀念珠菌活性，从而表明至少12个残基的肽链长度是引发最佳生物活性所必需的。这些线性肽的CD光谱表明，它们在结构上更灵活，并且它们根据溶剂环境采用不同的构象。CD研究提供的证据表明，组胺素5和较长的片段，C16，N16和C14在非水溶剂如三氟乙醇和甲醇中优选α-螺旋构象，而在水和pH 7.4的磷酸盐缓冲液中，它们有利于无规卷曲结构。较短的序列在水溶液和非水溶液中似乎采用转弯结构或无序结构。似乎在组胺素5的C-末端具有14个残基的最小链长和α-螺旋构象的序列是可观的杀念珠菌活性的重要结构要求。
Histatin 5 (Asp1-Ser-His-Ala4-Lys-Arg-His-His8-Gly-Tyr-Lys-Arg12-Lys-Ph e-His-Glu16-Lys-His - His-Ser20-His-Arg-Gly-Tyr24), one of the basic histidine-rich peptides present in human parotid saliva and several of its fragments, 1-16 (N16), 9-24 (C16), 11-24 (C14), 13-24 (C12), 15-24 (C10), and 7-16 (M10), were synthesized by solid-phase procedures. Native histatin 5 from human parotid saliva was also purified. Their antifungal activities on two strains of Candida albicans have been studied and their conformational preferences both in aqueous and non-aqueous solutions examined by circular dichroism. The synthetic histatin 5, C16, and C14 peptides were highly active and inhibited the growth of C. albicans. The candidacidal activity data of synthetic histatin 5 were comparable to the values of the native histatin 5 isolated from parotid saliva and those reported previously, although the assay system used and the strains examined were different. The C16 fragment was as active as the whole peptide itself, whereas the N16 fragment was far less active than C14, suggesting that the sequence at the C-terminal is important for its fungicidal activity. An increase in the chain length of the C-terminal sequence from 12 to 16 residues increased the candidacidal activity, thereby indicating that a peptide chain length of at least 12 residues is necessary to elicit optimum biological activity. The CD spectra of these linear peptides showed that they are structurally more flexible, and they adopt different conformations depending on the solvent environment. CD studies provided evidence that histatin 5 and the longer fragments, C16, N16, and C14 preferred alpha-helical conformations in non-aqueous solvents such as trifluoroethanol and methanol, while in water and pH 7.4 phosphate buffers, they favored random coil structures. The shorter sequences seemed to adopt either turn structures or unordered structures both in aqueous and non-aqueous solutions. It appears that the sequence at the C-terminal of histatin 5 with a minimum chain length of 14 residues and alpha-helical conformation are the important structural requirements for appreciable candidacidal activity.