PREPARATION OF MULTIFUNCTIONAL PEPTIDEPOLY (ETHYLENE GLYCOL) HYBRIDS

由于聚乙二醇（PEG）具有低毒性、低免疫原性和在水和有机溶剂中的良好溶解性，它似乎是一种有前途的药物载体。蛋白质聚乙二醇化修饰的研究已有很多报道，但小分子肽聚乙二醇化修饰的报道较少。我们成功地形成了小肽的PEG杂合体[如来源于纤连蛋白的RGD和来源于层粘连蛋白的YIGSR]，其导致母体肽的活性增强。位于市售PEG的每个末端的两个羟基是可以连接到两个相同肽的官能团。我们计划制备多功能PEG-肽杂合物（如-W-PEG-X-PEG-Y）。W，X，Y：不同的功能肽）。作为制备多功能PEG杂化物的第一步，我们成功地使用氨基酸型PEG（aaPEG）制备了双功能肽-PEG杂化物[X-PEG-Y（X，Y：不同的生物活性肽）]，所述氨基酸型PEG（aaPEG）由我们实验室中可商购的PEG制备。制备了RGD-PEG-EILDV和PDSGR-PEG-YIGSR，它们具有抗转移活性。

Since poly (ethylene glycol) (PEG) has a low toxicity, a low immunogenicity, and good solubility in both aqueous and organic solvents, it appears to be a promising drug-carrier. Many studies on pegylation of proteins have been reported, but few of them report on the pegylation of small peptides. We were successful in forming PEG hybrids of small peptides [such as RGD derived from fibronectin and YIGSR derived from laminin] that results in the potentiation of activity of the parent peptides. The two hydroxyl groups situated at each terminal of commercially available PEG are the functional group that can attach to two same peptides. We planned to prepare a multi-functional PEG-peptide hybrid (such as-W-PEG-X-PEG-Y. W, X, Y : different functional peptides) by conjugating different bioactive peptides with PEG. As a first step for preparation of a multifunctional PEG hybrid, we were successful in preparing bifunctional peptide-PEG hybrids [X-PEG-Y (X, Y : different bioactive peptides)] using an amino acid type PEG (aaPEG) which was prepared from a commercially available PEG in our laboratory. RGD-PEG-EILDV and PDSGR-PEG-YIGSR were prepared and they showed antimetastatic activity.