Isolation of a novel basic FGF-binding peptide with   potent antiangiogenetic activity.
Basic fibroblast growth factor (bFGF), which plays an important role in tumour angiogenesis and progression, provides a potential target for cancer therapy. Here we screened a phage display heptapeptide library with bFGF and identified 11 specific bFGF-binding phage clones. Two of these clones had identical sequence and the corresponding peptide (referred to as P7) showed high homology to the immunoglobulin-like (Ig-like) domain III (D3) of high-affinity bFGF receptors, FGFR1 (IIIc) and FGFR2 (IIIc). The P7 peptide and its corresponding motif in D3 of FGFRs both carried negative charges and shared similar hydrophobic profiles. Functional analysis demonstrated that synthetic P7 peptides mediate strong inhibition of bFGF-induced cell proliferation and neovascularization. Our results demonstrate that the P7 peptide is a potent bFGF antagonist with strong antiangiogenetic activity, and might have therapeutic potential in cancer therapy.
Wu
Xiaoping
X
School of Pharmaceutical Science, Key Laboratory of Biotechnology and Pharmaceutical Engineering of Zhejiang Province, Wenzhou Medical College, Wenzhou, China
Yan
Qiuxia
Q
Huang
Yadong
Y
Huang
Huixian
H
Su
Zhijian
Z
Xiao
Jian
J
Zeng
Yaoying
Y
Wang
Yi
Y
Nie
Changjun
C
Yang
Yongguang
Y
Li
Xiaokun
X
D016475:3T3 Cells; D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000502:physiology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
D020533:Angiogenesis Inhibitors; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C574793:prolyl-leucyl-leucyl-glutaminyl-alanyl-threonyl-leucine; D005346:Fibroblast Growth Factors