Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers
Design, synthesis, and characterization of a cationic peptide that binds to nucleic acids and permeabilizes bilayers
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DOI：
10.1021/bi9618474
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发表时间：
1997-03-11
期刊：
影响因子：
2.9
通讯作者：
Szoka, FC
中科院分区：
文献类型：
--
作者：
Wyman, TB;Nicol, F;Szoka, FC
我们设计了一种阳离子两亲性肽KALA（WEAKLAKALAKALAKHLAKALAKALKACEA），它与DNA结合，使膜不稳定，并介导DNA转染。当pH从5.0增加到7.5时，KALA经历pH依赖性无规卷曲到两亲性或螺旋构象的变化。一面显示疏水性亮氨酸残基，相对面显示亲水性赖氨酸残基。KALA介导的从中性和带负电荷的脂质体中释放截留的水性内容物随着螺旋内容物的增加而增加。KALA与寡核苷酸或质粒DNA结合，并阻碍它们在凝胶电泳中的迁移。它以0.9/1的电荷比（+/-）从DNA中置换50%的溴化乙锭。在培养的细胞中，当以10/1（+/-）电荷比制备复合物时，KALA协助寡核苷酸核递送。KALA/DNA（10/1）（+/-）复合物介导多种细胞系的转染。KALA序列提供了一个起点，一个家庭的肽，纳入其他功能，以改善DNA输送系统。
We have designed a cationic amphipathic peptide, KALA (WEAKLAKALAKALAKHLAKALAKALKACEA), that binds to DNA, destabilizes membranes, and mediates DNA transfection. KALA undergoes a pH-dependent random coil to amphipathic or-helical conformational change as the pH is increased from 5.0 to 7.5. One face displays hydrophobic leucine residues, and the opposite face displays hydrophilic lysine residues. KALA-mediated release of entrapped aqueous contents from neutral and negatively charged liposomes increases with increasing helical content. KALA binds to oligonucleotides or plasmid DNA and retards their migration in gel electrophoresis. It displaces 50% of ethidium bromide from DNA at a charge ratio (+/-) of 0.9/1. In cultured cells, KALA assists oligonucleotide nuclear delivery when complexes are prepared at a 10/1 (+/-) charge ratio. KALA/DNA (10/1) (+/-) complexes mediate transfection of a variety of cell lines. The KALA sequence provides a starting point for a family of peptides that incorporate other functions to improve DNA delivery systems.