Novel Cell‐Penetrating Peptides Based on α‐Aminoxy Acids
Novel Cell‐Penetrating Peptides Based on α‐Aminoxy Acids
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DOI：
10.1002/cbic.201100682
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发表时间：
2012-01
期刊：
影响因子：
3.2
通讯作者：
Yilong Ma;Dongmei Yang;Yan Ma;Yu-Hui Zhang
中科院分区：
文献类型：
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作者：
Yilong Ma;Dongmei Yang;Yan Ma;Yu-Hui Zhang
细胞穿透肽（CPP）将细胞不可渗透的化合物递送到活细胞中的显著能力使其成为用于生物学和医学的有吸引力的转运蛋白。尽管其高效的细胞摄取，由天然氨基酸组成的CPP总是遭受降解和内体截留，从而极大地限制了其在体内的应用。在这里，我们描述了新的CPP的制备纳入α-氨氧基酸残基和它们的细胞摄取行为。我们证明，在CPP的主链中引入α-氨基氧基酸增强了其在直接膜易位后的弥散性胞质分布。我们还揭示了由D-α-氨基氧基酸和L-α-氨基酸组成的杂合肽，其在胞质溶胶中实现有效的扩散分布，对血清稳定，并且具有低细胞毒性，从而使其成为体内应用的可能载体候选物。我们的研究结果证实，α-氨基氧基酸是有用的积木时，设计具有良好的性能的新型CPP。
The remarkable ability of cell‐penetrating peptides (CPPs) to deliver cell‐impermeable compounds into living cells makes them attractive transporters for use in biology and medicine. Despite their highly efficient cellular uptake, CPPs consisting of natural amino acids always suffer from degradation and endosomal entrapment, thereby greatly limiting their application in vivo. Here, we describe the preparation of novel CPPs incorporating α‐aminoxy acid residues and their cellular uptake behavior. We demonstrate that introducing α‐aminoxy acids into the backbones of CPPs enhances their diffuse cytosolic distribution after direct membrane translocation. We also reveal a hybrid peptide, consisting of D‐α‐aminoxy acids and L‐α‐amino acids, that achieves efficient diffuse distribution in the cytosol, is stable toward serum, and possesses low cytotoxicity, thus making it a possible vector candidate for in vivo applications. Our results confirm that α‐aminoxy acids are useful building blocks when designing novel CPPs possessing favorable properties.