Preparation and Biological Activities of a Bivalent Poly(Ethylene Glycol) Hybrid Containing an Active Site and Its Synergistic Site of Fibronectin

• Published in: Chemical & pharmaceutical bulletin Vol. 50; no. 9; pp. 1229 - 1232
• Main Authors: Susuki, Yuichi, Hojo, Keiko, Okazaki, Ikuko, Kamata, Haruhiko, Sasaki, Masahiko, Maeda, Mitsuko, Nomizu, Motoyoshi, Yamamoto, Yoko, Nakagawa, Shinsaku, Mayumi, Tadanori, Kawasaki, Koichi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.09.2002; Japan Science and Technology Agency
• Subjects: Amino Acids - chemistry; Animals; anti-metastatic activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binding Sites; Cell Survival; Chromatography, High Pressure Liquid; Cricetinae; fibronectin; Fibronectins - chemistry; hybrid; Indicators and Reagents; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Neoplasm Metastasis - pathology; Neoplasm Metastasis - prevention & control; Neoplasm Transplantation; poly(ethylene glycol); Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; spreading activity
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.50.1229

A bivalent poly(ethylene glycol) or PEG hybrid of fibronectin-related peptides was prepared. An active site peptide (RGD) and its synergistic site peptide (PHSRN) of fibronectin were conjugated with an amino acid-type PEG (aaPEG) to form PHSRN–aaPEG–RGD. A moderate spatial array between RGD and PHSRN in fibronectin may be required for synergic activity. The bivalent hybrid exhibited potent cell spreading activity and exhibited potent anti-metastatic activity in a model of experimental metastasis with B16–BL6 cells in mice. PEG may serve as a spacer for maintaining the desired spatial array.