The pH sensitivity of histidine-containing lytic peptides.

The pH sensitivity of histidine-containing lytic peptides.
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DOI:
10.1002/psc.1180
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发表时间:
2009-11
影响因子:
2.1
通讯作者:
Liang, Jun F.
Liang, Jun F.
中科院分区:
生物学4区
文献类型:
--
作者:
Tu, Zhigang;Young, Albert;Murphy, Christopher;Liang, Jun F.

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许多生物活性肽因其独特的氨基酸组成而具有特色,例如富含精氨酸/赖氨酸的肽。然而,富含组氨酸的生物活性肽却很少见。在这项研究中,通过用组氨酸选择性地替换裂解肽LL - 1中相应的赖氨酸残基来构建含组氨酸的肽。有趣的是,所有所得肽都表现出pH依赖性活性。当溶液的pH从7.4降至5.5时,这些肽的细胞裂解活性可提高多达四倍。含组氨酸肽的pH敏感性由组氨酸取代数量决定。含有更多组氨酸的肽衍生物具有更高的pH敏感性。结果表明,含组氨酸肽的pH依赖性活性并非由二级结构决定,而是由pH影响的细胞亲和力变化所致。这里展示的组氨酸取代方法可能为构建具有所需pH敏感性的生物活性肽以用于各种应用提供一种通用策略。
Many bioactive peptides are featured by their unique amino acid compositions such as argine/lysine-rich peptides. However, histidine-rich bioactive peptides are hardly found. In this study, histidine-containing peptides were constructed by selectively replacing the corresponded lysine residues in a lytic peptide LL-1 with histidines. Interestingly, all resulting peptides demonstrated pH-dependent activities. The cell lysis activities of these peptides could be increased up to four times as the solution pHs dropped from pH=7.4 to pH=5.5. The pH sensitivity of a histidine-containing peptide was determined by histidine substitution numbers. Peptide derivatives with more histidines were associated with increased pH sensitivity. Results showed that not the secondary structures but pH-affected cell affinity changes were responsible for the pH-dependent activities of histidine-containing peptides. The histidine substitution approach demonstrated here may present a general strategy to construct bioactive peptides with desired pH sensitivity for various applications.
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