Klaikherd Akamol, Sandanaraj Britto S, Vutukuri Dharma Rao, Thayumanavan S
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA.
J Am Chem Soc. 2006 Jul 19;128(28):9231-7. doi: 10.1021/ja0622406.
Facially amphiphilic biaryl dendrimers are compared with the more classical benzyl ether amphiphilic dendrimers for molecular recognition, using protein binding as the probe. The protein used for the proposed study is chymotrypsin (ChT). A generation-dependent binding affinity was observed with the benzyl ether dendrimers, while the affinities were independent of generation in the case of the biaryl dendrimers. Similarly, although the ligands incorporated in both dendrons are the same, the biaryl dendrimers are able to bind more proteins compared to the benzyl ether dendrimers. For example, G3-dendron of biaryl dendrimer can bind six molecules of chymotrypsin, whereas G3-analogue of benzyl ether dendrimers can bind only three molecules of chymotrypsin. This result is consistent with our hypothesis that the internal layers of the facially amphiphilic biaryl dendrons are solvent-exposed and accessible for recognition. In addition, the systematic size differences in dendrons were also used to gain insights into the substrate selectivity that the enzyme gains upon binding to a ligand scaffold.
以蛋白质结合为探针，将表面两亲性联芳基树枝状大分子与更经典的苄基醚两亲性树枝状大分子进行分子识别比较。拟用于该研究的蛋白质是胰凝乳蛋白酶（ChT）。观察到苄基醚树枝状大分子具有与代数相关的结合亲和力，而联芳基树枝状大分子的亲和力与代数无关。同样，尽管两种树枝状分子中掺入的配体相同，但与苄基醚树枝状大分子相比，联芳基树枝状大分子能够结合更多的蛋白质。例如，联芳基树枝状大分子的G3树枝状分子可以结合六个胰凝乳蛋白酶分子，而苄基醚树枝状大分子的G3类似物只能结合三个胰凝乳蛋白酶分子。这一结果与我们的假设一致，即表面两亲性联芳基树枝状分子的内层暴露于溶剂中且可用于识别。此外，树枝状分子的系统尺寸差异也被用于深入了解酶与配体支架结合后获得的底物选择性。
