Engineering a noncarrier to a highly efficient carrier peptide for noncovalently delivering biologically active proteins into human cells
Engineering a noncarrier to a highly efficient carrier peptide for noncovalently delivering biologically active proteins into human cells
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DOI：
10.1016/j.ab.2007.03.020
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发表时间：
2007-06-15
影响因子：
2.9
通讯作者：
Sarkar, Gobinda
中科院分区：
文献类型：
--
作者：
Mahlitin, Eric;Mandal, Deendayal;Sarkar, Gobinda
通过肽载体将非共价蛋白质递送到细胞中是一个新兴的概念。只有少数这样的肽是已知的。为了解决与用于治疗目的的蛋白质递送相关的各种限制，将需要更多数量的不同递送肽。不存在用于产生此类肽的通用方法。通过将16个赖氨酸残基的序列（K16）与卡波西成纤维细胞生长因子（K-FGF）的信号肽（SP）序列组合，我们合成了一种肽（K16 SP），其有效地且非共价地将功能完整的蛋白质（免疫球蛋白G分子、β-半乳糖苷酶和绿色荧光蛋白）递送到哺乳动物细胞中。肽K16和SP各自单独不显示任何非共价蛋白质携带能力。K16 SP似乎对细胞无毒，并且比市售肽试剂的效率高三到四倍。我们的方法为最终的治疗应用提供了一种创建多种肽载体的一般策略的概念验证。(c)2007年爱思唯尔公司All rights reserved.
Noncovalent protein delivery into cells via peptide carriers is an emerging concept. Only a handful of such peptides are known. To address various limitations associated with protein delivery for therapeutic purposes, a greater number of different delivery peptides would be required. No general method exists for creating such peptides. By combining a sequence of 16 lysine residues (K16) with the signal peptide (SP) sequence of Kaposi's fibroblast growth factor (K-FGF), we have synthesized a peptide (K16SP) that efficiently and noncovalently delivers functionally intact proteins (immunoglobulin G molecules, beta-galactosidase, and green fluorescent protein) into mammalian cells. The peptides K16 and SP each alone did not show any noncovalent protein-carrying capacity. K16SP appears to be nontoxic to cells and three to four times more efficient than a commercially available peptide reagent. Our approach offers proof-of-concept of a general strategy for creating a diverse array of peptide carriers for eventual therapeutic applications. (c) 2007 Elsevier Inc. All rights reserved.