Huang S Y, Pooyan S, Wang J, Choudhury I, Leibowitz M J, Stein S
Center for Advanced Biotechnology and Medicine and Chemistry Department, Rutgers University, New Brunswick, New Jersey 08903-2101, USA.
Bioconjug Chem. 1998 Sep-Oct;9(5):612-7. doi: 10.1021/bc980038p.
Two different methods were developed to prepare an adduct of a poly(ethylene glycol)-lysine copolymer with either cysteamine or 1-amino-2-methyl-2-propanethiol. Cysteine-containing peptides could then be disulfide-linked to the thiol groups on the polymer in a facile manner. In the described procedures, a coupling ratio of about 8 peptides/molecule of poly(ethylene glycol)-lysine copolymer (Mw = 27 000) was typically attained. The products were stable at neutral pH, but the peptides could be released from the polymer in a physiologically relevant reducing environment. The release rate was highly dependent on the linker used for forming the disulfide bond. To illustrate the potential biomedical usefulness of this polymer carrier, a Tat peptide-PEG conjugate was shown to inhibit expression of a reporter gene fused to the TAR element of human immunodeficiency virus in a model cell assay.
已开发出两种不同的方法来制备聚乙二醇 - 赖氨酸共聚物与半胱胺或1 - 氨基 - 2 - 甲基 - 2 - 丙硫醇的加合物。然后，含半胱氨酸的肽可以以简便的方式通过二硫键连接到聚合物上的硫醇基团。在所描述的程序中，通常可实现约8个肽/聚乙二醇 - 赖氨酸共聚物分子（Mw = 27000）的偶联比。产物在中性pH下稳定，但在生理相关的还原环境中，肽可以从聚合物中释放出来。释放速率高度依赖于用于形成二硫键的连接子。为了说明这种聚合物载体潜在的生物医学用途，在模型细胞试验中，一种Tat肽 - PEG缀合物被证明可抑制与人类免疫缺陷病毒TAR元件融合的报告基因的表达。
