Potential peptide carriers:: Amphipathic proline-rich peptides derived from the n-terminal domain of γ-zein
Potential peptide carriers:: Amphipathic proline-rich peptides derived from the n-terminal domain of γ-zein
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DOI：
10.1002/anie.200352540
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Giralt, E
中科院分区：
文献类型：
--
作者：
Fernández-Carneado, J;Kogan, MJ;Giralt, E
某些多肽穿越真核细胞膜的能力显然是药物传递领域的兴趣所在。近年来，这种兴趣导致了肽载体的快速发展，用于递送抗肿瘤、抗病毒或抗生素药物，否则这些药物将无法穿过细胞膜到达其治疗靶点。使用肽载体的其他优点包括其毒性低，易于合成，并且在将肽或小分子药物作为货物时具有很高的修饰灵活性多种短肽作为载体[2]在细胞内传递多肽、[3]蛋白、[4]或寡核苷酸[5]的能力已被证实，而最近的研究已经确定的肽载体包括：人降钙素（hCT）、[6]蛋白转导域片段（VP22、[7]Tat、[8]或Antp[9]）、富含精氨酸的肽、[10]b-肽、[11]类肽、[12]和低聚物[13]尽管人们对这种易位过程的机制知之甚少，但决定自组装的载体的两亲性似乎对分子与受体（分子识别）或与高度两亲性环境的相互作用至关重要富含脯氨酸的抗生素穿过细胞膜的能力也已被证实，最近我们报道了一个令人惊讶的结果，即一种仅含有脯氨酸残基的肽（P14）穿过细胞膜，尽管效率很低在纯水中，聚脯氨酸采用一种明确的二级结构，即聚脯氨酸II (PPII)，但与a-螺旋不同，PPII是左旋的，每转3.0个残基。将PPII螺旋转化为两亲螺旋的规则
The ability of certain peptides to cross eukaryotic cell membranes is clearly of interest in the drug delivery field. In recent years, this interest has led to the rapid development of peptide carriers for the delivery of antitumoral, antiviral, or antibiotic drugs, which otherwise would be unable to cross the cell membrane and reach their therapeutic target. Additional advantages of the use of peptide carriers include their low toxicity, accessible synthesis, and high flexibility for modification when attaching peptides or small-molecule drugs as cargoes.[1] The ability of a wide variety of short peptides to act as carriers [2] for the delivery of peptides,[3] proteins,[4] or oligonucleotides [5] inside the cell has been demonstrated, while recent studies have identified peptide vectors including: human calcitonin (hCT),[6] fragments of protein-transduction domains (VP22,[7] Tat,[8] or Antp [9]), arginine-rich peptides,[10] b-peptides,[11] peptoids,[12] and loligomers.[13] Although little is known about the mechanism that operates in a translocation process of this nature, the amphipathicity of the carriers, which determines self-assembly, appears to be crucial for the interaction of the molecules with receptors (molecular recognition) or with highly amphipathic environments.[14] The ability of proline-rich antibiotics to cross the cell membrane has also been demonstrated [15] and recently we reported the surprising result that a peptide containing only proline residues (P14) crossed the cell membrane, albeit with low efficiency.[16] Polyprolines adopt a well defined secondary structure, polyproline II (PPII), in pure water but unlike the a-helix, PPII is left-handed with 3.0 residues per turn. The rules for transforming a PPII helix into an amphipathic helix