Deletion analogues of transportan
Deletion analogues of transportan
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DOI：
10.1016/s0005-2736(00)00216-9
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发表时间：
2000-07-31
影响因子：
3.4
通讯作者：
Langel, Ü
中科院分区：
文献类型：
--
作者：
Soomets, U;Lindgren, M;Langel, Ü
已经合成了细胞穿透肽转运蛋白的几种较短的类似物，以定义负责肽的膜易位性质的序列区域。已经测试了肽渗透到Bowes黑素瘤细胞中以及对Pin m5 F细胞膜中的GTdR活性的影响。细胞渗透的实验数据进行了比较与分子建模插入到生物膜的肽。从N-末端的6个氨基酸的省略没有显着损害的肽的细胞渗透，而在C-末端或在中间的转运蛋白序列的缺失减少或取消的细胞摄取。大多数转运蛋白类似物对GT3活性具有抑制作用。分子模拟表明，插入的转运蛋白类似物到膜不同的肽。可能肽的长度以及芳香族和带正电荷的残基的位置对肽在膜中的取向具有主要影响，从而影响细胞渗透。总之，我们已经设计并表征了几种新的短转运蛋白类似物，其具有与亲本肽相似的细胞易位性质，但具有降低的不期望的细胞活性。(C)2000 Elsevier Science B. V.保留所有权利。
Several shorter analogues of the cell penetrating peptide, transportan, have been synthesized in order to define the regions of the sequence, which are responsible for the membrane translocation property of the peptide. Penetration of the peptides into Bowes melanoma cells and the influence on GTPase activity in Pin m5F cellular membranes have been tested. The experimental data on cell penetration have been compared with molecular modeling of insertion of peptides into biological membranes. Omission of six amino acids from the N-terminus did not significantly impair the cell penetration of the peptide while deletions at the C-terminus or in the middle of the transportan sequence decreased or abolished the cellular uptake. Most transportan analogues exert an inhibitory effect on GTPase activity. Molecular modeling shows that insertion of the transportan analogues into the membrane differs for different peptides. Probably the length of the peptide as well as the location of aromatic and positively charged residues have major impact on the orientation of peptides in the membranes and thereby influence the cellular penetration. In summary, we have designed and characterized several novel short transportan analogues with similar cellular translocation properties to the parent peptide, but with reduced undesired cellular activity. (C) 2000 Elsevier Science B.V. All rights reserved.