University of Notre Dame, Department of Chemical & Biomolecular Engineering, Notre Dame, Indiana 46556 United States.
Bioconjug Chem. 2022 Dec 21;33(12):2262-2268. doi: 10.1021/acs.bioconjchem.2c00242. Epub 2022 Jul 8.
The affinity possible from certain supramolecular motifs rivals that for some of the best-recognized interactions in biology. Cucurbit[7]uril (CB[7]) macrocycles, for example, are capable of achieving affinities in their binding to certain guests that rival that of biotin-avidin. Supramolecular host-guest recognition between CB[7] and certain guests has been demonstrated to spatially localize guest-linked agents to desired sites , offering opportunities to better exploit this affinity axis for applications in biomedicine. Herein, architectures of CB[7] are prepared from a polyamidoamine (PAMAM) dendrimer scaffold, installing a PEG-linked cholesterol anchor on the opposite end of the dendron to facilitate cell membrane integration. Cells are then modified with this dendritic CB[7] construct , demonstrating the ability to deliver a model guest-linked agent to the cell membrane. This approach to realize synthetic supramolecular "membrane receptors" may be leveraged in the future for imaging or modulation of cell-based therapies or to facilitate a synthetic supramolecular recognition axis on the cell membrane.
某些超分子结构所具有的亲和力可与生物学中一些最知名的相互作用相媲美。例如，葫芦[7]脲（CB[7]）大环能够与某些客体形成亲和力，与生物素-亲和素的亲和力相当。已经证明 CB[7]和某些客体之间的超分子主体-客体识别能够将与客体相连的试剂定位在所需的部位，为在生物医学中应用这一亲和力轴提供了机会。在此，通过聚酰胺-胺（PAMAM）树枝状大分子支架制备 CB[7]的结构，在树枝的相反端安装连接 PEG 的胆固醇锚，以促进细胞膜的整合。然后用这种树枝状 CB[7]结构修饰细胞，证明能够将模型客体连接的试剂递送到细胞膜。这种实现合成超分子“膜受体”的方法可在未来用于成像或调节基于细胞的治疗方法，或促进细胞膜上的合成超分子识别轴。
