A new class of “polymultivalent” ligands combining several ligand clusters and a water-soluble biocompatible polymer is introduced. These original conjugates bear two levels of multivalency. They are prepared by covalent coupling of a controlled number of tetrameric cRGD peptide clusters along a well-defined copolymer synthesized by RAFT polymerization. The presence of multiple copies of peptide clusters on the same polymer backbone resulted in a much-higher relative potency than the free cluster reference. Thanks to the “polymultivalency”, up to ∼2 orders of magnitude potency enhancement was reached in a competitive cell adhesion assay (nanomolar-range IC₅₀ values). In addition, confocal microscopy and flow cytometry demonstrated that fluorescent “polymultivalent” conjugates (emitting in the far-red/near-infrared region) were able to specifically and selectively label cells expressing α_vβ₃-integrin, the natural receptor of cRGD.

中文翻译：

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“Polymultivalent”聚合物-肽缀合物集群用于表达α细胞增强的靶向_v β _3点整联蛋白

引入了一种新的“多价”配体，该配体结合了多个配体簇和一种水溶性生物相容性聚合物。这些原始共轭物具有两个水平的多价。它们是通过将一定数量的四聚体cRGD肽簇沿着通过RAFT聚合合成的定义明确的共聚物共价偶联而制备的。在同一聚合物主链上存在多个拷贝的肽簇，其相对效价比游离簇参照物高得多。由于具有“多价性”，在竞争性细胞粘附试验（纳摩尔级IC _50）中，效价提高了约2个数量级。值）。此外，共聚焦显微镜和流式细胞仪证实荧光“polymultivalent”缀合物（在远红/近红外区域发光）能够表达α特异性和选择性标记的细胞_v β ₃整合素，的cRGD的天然受体。