Preparation and biological activities of a bivalent poly(ethylene glycol) hybrid containing an active site and its synergistic site of fibronectin.
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.
Susuki
Yuichi
Y
Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University, Japan.
Hojo
Keiko
K
Okazaki
Ikuko
I
Kamata
Haruhiko
H
Sasaki
Masahiko
M
Maeda
Mitsuko
M
Nomizu
Motoyoshi
M
Yamamoto
Yoko
Y
Nakagawa
Shinsaku
S
Mayumi
Tadanori
T
Kawasaki
Koichi
K
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D005353:Fibronectins / Q000737:chemistry*; D007202:Indicators and Reagents; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000596:Amino Acids; D000970:Antineoplastic Agents; D005353:Fibronectins; D007202:Indicators and Reagents; D011092:Polyethylene Glycols