Rationally designed peptides for controlled release of nerve growth factor from fibrin matrices
Rationally designed peptides for controlled release of nerve growth factor from fibrin matrices
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DOI：
10.1002/jbm.a.30844
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发表时间：
2007-01-01
影响因子：
4.9
通讯作者：
Sakiyama-Elbert, Shelly E.
中科院分区：
文献类型：
--
作者：
Willerth, Stephanie M.;Johnson, Philip J.;Sakiyama-Elbert, Shelly E.
本研究的目的是鉴定与神经生长因子(NGF)具有不同亲和力的多肽序列，并将其用于基于亲和力的药物递送系统的合理设计。用NGF-偶联层析树脂对噬菌体展示文库(12个氨基酸随机肽序列)进行了3次筛选，并通过降低洗脱液的pH洗脱了不同亲和力的噬菌体部分。这些噬菌体被分离、扩增，然后对它们的DNA进行纯化和测序，以确定随机肽结构域的身份。合成了基于这些序列的共识多肽，并对它们与NGF结合的能力进行了筛选，并以不同的速度从纤维蛋白基质中释放NGF。使用鸡背根神经节模型测试了含有这些多肽和NGF的纤维蛋白基质向生物活性NGF传递的能力。为了进一步了解多肽的亲和力如何调节NGF的释放，并帮助优化递送系统的设计，开发了一个数学模型。这项研究中确定的多肽对NGF具有不同的亲和力，这表明这种方法可以作为一种模型，用于调整药物输送系统对目标蛋白药物的亲和力。(C)2006年威利期刊公司。
The purpose of this research was to identify peptide sequences with varying affinity for nerve growth factor (NGF) and use them in the rational design of affinity-based drug delivery systems. A phage display library (12 amino acid random peptide sequence) was screened against NGF-conjugated chromatography resin three times and fractions containing phage of varying affinity were eluted by decreasing the pH of the eluent. These phages were isolated, amplified; then their DNA was purified and sequenced to determine the identity of the random peptide domain. Consensus peptides based on these sequences were synthesized and screened for their ability to bind NGF and release it at different rates from fibrin matrices. The ability of fibrin matrices containing these peptides and NGF to deliver to biologically active NGF was tested using a chick dorsal root ganglia model. A mathematical model was developed to further understand how the affinity of a peptide can modulate release of NGF and to aid in design optimization for the delivery system. The peptides identified in this study were determined to have varying affinities for NGF suggesting that this approach can serve as a model for tailoring the affinity of a drug delivery system for a target protein drug. (c) 2006 Wiley Periodicals, Inc.