Constructing bioactive peptides with pH-dependent activities.

Constructing bioactive peptides with pH-dependent activities.
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DOI:
10.1016/j.peptides.2009.05.009
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发表时间:
2009-08
期刊:
影响因子:
3
通讯作者:
Liang JF
Liang JF
中科院分区:
医学3区
文献类型:
--
作者:
Tu Z;Volk M;Shah K;Clerkin K;Liang JF

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许多生物活性肽的特点是富含精氨酸和赖氨酸。在这项研究中,裂解肽中的赖氨酸和精氨酸残基被组氨酸选择性取代。尽管所得含组氨酸的裂解肽活性降低,但它们确实显示出pH依赖性细胞毒性。当溶液pH从7.4变为5.5时,构建的含组氨酸裂解肽的活性增加了2 - 8倍。更重要的是,这些含组氨酸的肽通过引起细胞裂解,保持了与其母体肽相同的细胞杀伤机制。含组氨酸肽的活性和pH敏感性均可通过调整组氨酸取代的数量和位置来调节。这项研究提出了一种通用策略,用于创建具有所需pH敏感性的生物活性肽,以满足癌症治疗等各种应用的需求。
Many bioactive peptides are featured by their arginine and lysine rich contents. In this study, lysine and arginine residues in lytic peptides were selectively replaced by histidines. Although resulted histidine-containing lytic peptides had decreased activity, they did show pH-dependent cytotoxicity. The activity of the constructed histidine-containing lytic peptides increased 2 ~ 8 times as the solution pH changed from of 7.4 to 5.5. More importantly, these histidine-containing peptides maintain the same cell killing mechanism as their parent peptides by causing cell lysis. Both the activity and pH-sensitivity of histidine-containing peptides are tunable by adjusting histidine substitution numbers and positions. This study has presented a general strategy to create bioactive peptides with desired pH-sensitivity to meet the needs of various applications such as cancer treatments.
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