Constructing bioactive peptides with pH-dependent activities.

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.

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。