PREPARATION OF MULTIFUNCTIONAL PEPTIDEPOLY (ETHYLENE GLYCOL) HYBRIDS

多功能肽聚（乙二醇）杂化物的制备

• 批准号: 09672291
• 负责人: KAWASAKI Koichi
• 金额: $ 1.98万
• 依托单位: KOBE GAKUIN UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672291/
• 关键词: POLY (ETHYLENE GLYCOL); DRUG CARRIER; LAMININ; FIBRONECTIN; 癌転移; 高分子担体; 細胞接着タンパク質

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.

聚乙二醇具有低毒、低免疫原性、在水和有机溶剂中均有良好的溶解性等优点，是一种很有前途的药物载体。关于蛋白质的聚乙二醇化已有很多报道，但很少有关于小肽的聚乙二醇化的报道。我们成功地形成了小肽[如来自纤维连接蛋白的RGD和来自层粘连蛋白的YIGSR]的聚乙二醇杂交物，从而增强了亲本多肽的活性。位于市场上可买到的聚乙二醇的每个末端的两个羟基是可以结合到两个相同的多肽上的官能团。我们计划制备一种多功能的聚乙二醇-多肽杂交物(如-W-聚乙二醇-X-聚乙二醇-Y。W，X，Y：不同的功能多肽)。作为制备多功能聚乙二醇杂交物的第一步，我们成功地利用我们实验室从商品化聚乙二醇制得的氨基酸型聚乙二醇酯(AaPEG)制备了双功能肽-聚乙二醇杂交物[X-PEGY(X，Y：不同的生物活性多肽)]。制备了RGD-PEG-EILDV和PDSGR-PEG-YIGSR，并显示了一定的抗肿瘤活性。

项目成果

Mitsuko Maeda: "Amino Acids and Peptides. XXXI. Preparation of Analogs of the Laminin-Related Peptides"Chem.Pharm. Bull.. 45(11). 1788-1792 (1997)

Mitsuko Maeda：“氨基酸和肽。XXXI.层粘连蛋白相关肽类似物的制备”Chem.Pharm。

Mitsuko Maeda: "Amino Acids and Peptides. XXX. Preparation of Arg-Gly-Asp(RGD)Hybrids with Poly(えthylene Glycol)Analogs and Their Antimetastatic Effect"Chem.Pharm. Bull.. 45(11). 1788-1792 (1997)

Mitsuko Maeda：“氨基酸和肽。XXX。用聚(乙二醇)类似物制备精氨酸-甘氨酸-天冬氨酸(RGD)杂化物及其抗转移作用”Chem.Pharm. 45(11)。 1997)

Keiko Hojo: "Preparation of a Chitosan Hybrid of an Antimetastatic Laminin-related Peptide"Pharm. Pharmacol. Commun.. #5. 277-280 (1999)

Keiko Hojo：“抗转移层粘连蛋白相关肽的壳聚糖杂合体的制备”药学。

Yu Mu: "Bioconjugation of Laminin Peptide YIGSR with Poly (Styrene Co-maleic Acid) Increase Its Antimetastatic Effect on Lung Metastasis of B16-BL6 Melanoma Cells"Biochem. Biophys. Res. Commun.. 255(2). 75-79 (1999)

于穆：“层粘连蛋白肽YIGSR与聚(苯乙烯-马来酸)的生物共轭增加其对B16-BL6黑色素瘤细胞肺转移的抗转移作用”Biochem。

Mitsuko Maeda: "Amino Acids and Peptides. XXXII. A Bifunctional Poly (Ethylene Glycol) Hybrid of Fibronectin-Related Peptides."Biochem. Biophys. Res. Commun.. 241(2). 595-598 (1997)

Mitsuko Maeda：“氨基酸和肽。XXXII。纤连蛋白相关肽的双功能聚（乙二醇）杂合体。”Biochem。