Isolation of a novel basic FGF-binding peptide with potent antiangiogenetic activity.

Isolation of a novel basic FGF-binding peptide with potent antiangiogenetic activity.
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DOI:
10.1111/j.1582-4934.2008.00506.x
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发表时间:
2010-01
影响因子:
5.3
通讯作者:
Li X
Li X
中科院分区:
医学2区
文献类型:
--
作者:
Wu X;Yan Q;Huang Y;Huang H;Su Z;Xiao J;Zeng Y;Wang Y;Nie C;Yang Y;Li X

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碱性成纤维细胞生长因子(bFGF)在肿瘤血管生成和进展中发挥重要作用,为癌症治疗提供了潜在的靶点。在这里,我们筛选了带有 bFGF 的噬菌体展示七肽文库,并鉴定了 11 个特定的 bFGF 结合噬菌体克隆。其中两个克隆具有相同的序列,相应的肽(称为 P7)与高亲和力 bFGF 受体 FGFR1 (IIIc) 和 FGFR2 (IIIc) 的免疫球蛋白样(Ig 样)结构域 III (D3) 表现出高度同源性。 P7 肽及其在 FGFR D3 中的相应基序均携带负电荷并具有相似的疏水性特征。功能分析表明,合成的 P7 肽可强烈抑制 bFGF 诱导的细胞增殖和新血管形成。我们的结果表明,P7 肽是一种有效的 bFGF 拮抗剂,具有很强的抗血管生成活性,并且可能在癌症治疗中具有治疗潜力。
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.
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