Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
Org Biomol Chem. 2011 Jul 7;9(13):4795-801. doi: 10.1039/c1ob05241a. Epub 2011 May 17.
This paper compares covalent and non-covalent approaches for the organisation of ligand arrays to bind integrins. In the covalent strategy, linear RGD peptides are conjugated to first and second generation dendrons, and using a fluorescence polarisation competition assay, the first generation compound is demonstrated to show the most effective integrin binding, with an EC(50) of 125 μM (375 μM per peptide unit). As such, this dendritic compound is significantly more effective than a monovalent ligand, which does not bind integrin, even at concentrations as high as 1 mM. However, the second generation compound is significantly less effective, demonstrating that there is an optimum ligand density for multivalency in this case. In the non-covalent approach to multivalency, the same RGD peptide is functionalised with a hydrophobic C12 chain, giving rise to a lipopeptide which is demonstrated to be capable of self-assembly. This lipopeptide is capable of effective integrin binding at concentrations of 200 μM. These results therefore demonstrate that covalent (dendritic) and non-covalent (micellar self-assembly) approaches have, in this case, comparable efficiency in terms of achieving multivalent organisation of a ligand array.
本文比较了将配体阵列组织为结合整合素的共价和非共价方法。在共价策略中，线性 RGD 肽与第一代和第二代树状聚合物连接，并且使用荧光偏振竞争测定，第一代化合物被证明具有最有效的整合素结合，EC（50）为 125 μM（每个肽单位 375 μM）。因此，与不结合整合素的单价配体相比，这种树枝状化合物的效果明显更好，即使在高达 1 mM 的浓度下也是如此。然而，第二代化合物的效果明显较差，表明在这种情况下，多价结合存在最佳配体密度。在多价的非共价方法中，相同的 RGD 肽用疏水性 C12 链官能化，得到能够自组装的脂肽。这种脂肽能够在 200 μM 的浓度下有效结合整合素。因此，这些结果表明，在这种情况下，共价（树枝状）和非共价（胶束自组装）方法在实现配体阵列的多价组织方面具有相当的效率。
