Combinatorial chemistry identifies high-affinity peptidomimetics against alpha4beta1 integrin for in vivo tumor imaging.
Combinatorial chemistry identifies high-affinity peptidomimetics against alpha4beta1 integrin for in vivo tumor imaging.
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发表时间：
2006
影响因子：
14.8
通讯作者：
Li Peng;Ruiwu Liu;J. Mařík;Xiaobing Wang;Y. Takada;K. Lam
中科院分区：
文献类型：
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作者：
Li Peng;Ruiwu Liu;J. Mařík;Xiaobing Wang;Y. Takada;K. Lam
基于小肽的药物作为用于诊断成像和靶向治疗的癌症靶向药物引起了广泛的兴趣。需要开发针对癌细胞表面受体的新的高亲和力和高特异性的拟肽或小分子配体。在此，我们报告了使用多样化且高度集中的一珠一化合物组合拟肽文库并结合高严格筛选，鉴定了针对 α4β1 整联蛋白的高亲和力拟肽配体（LLP2A；IC50 = 2 pM）。我们进一步证明，当在小鼠异种移植模型中与近红外荧光染料缀合时，LLP2A 可用于以高灵敏度和特异性对表达 alpha4beta1 的淋巴瘤进行成像。因此，LLP2A为肿瘤进展过程中α4β1表达和活性的无创监测提供了重要工具，并且它显示出作为α4β1阳性肿瘤的成像和治疗剂的巨大潜力。
Small peptide-based agents have attracted wide interest as cancer-targeting agents for diagnostic imaging and targeted therapy. There is a need to develop new high-affinity and high-specificity peptidomimetic or small-molecule ligands against cancer cell surface receptors. Here we report on the identification of a high-affinity peptidomimetic ligand (LLP2A; IC50 = 2 pM) against alpha4beta1 integrin using both diverse and highly focused one-bead-one-compound combinatorial peptidomimetic libraries in conjunction with high-stringency screening. We further demonstrate that LLP2A can be used to image alpha4beta1-expressing lymphomas with high sensitivity and specificity when conjugated to a near infrared fluorescent dye in a mouse xenograft model. Thus, LLP2A provides an important tool for noninvasive monitoring of alpha4beta1 expression and activity during tumor progression, and it shows great potential as an imaging and therapeutic agent for alpha4beta1-positive tumors.