Mendez Luz C, Boadi Francis O, Kennedy Mitchell, Bhatia Surita R, Sampson Nicole S
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.
Department of Chemistry, University of Rochester, Rochester, New York 14627-0216, United States.
ACS Bio Med Chem Au. 2024 May 28;4(4):214-225. doi: 10.1021/acsbiomedchemau.4c00018. eCollection 2024 Aug 21.
A myriad of biological processes are facilitated by ligand-receptor interactions. The low affinities of these interactions are typically enhanced by multivalent engagements to promote binding. However, each biological interaction requires a unique display and orientation of ligands. Therefore, the availability and diversity of synthetic multivalent probes are invaluable to the investigation of ligand-receptor binding interactions. Here, we report glycopolymers prepared from bicyclo[4.2.0]oct-6-ene-7-carboxamide and 4,7-dihydro-1,3-dioxepin or cyclohexene. These glycopolymers, synthesized by alternating ring-opening metathesis polymerization, display precise ligand spacing as well as the option of a hydrophobic or acetal-functionalized polymer backbone. Small-angle X-ray scattering (SAXS) data analysis revealed that these [4.2.0] glycopolymers adopted distinct conformations in solution. In aqueous media, [4.2.0]-dioxepin glycopolymers formed swollen polymer chains with rod-like, flexible structures while [4.2.0]-cyclohexene glycopolymers assumed compact, globular structures. To illustrate how these glycopolymers could aid in the exploration of ligand-receptor interactions, we incorporated the [4.2.0] glycopolymers into a biological assay to assess their potential as activators of acrosomal exocytosis (AE) in mouse sperm. The results of the biological assay confirmed that the differing structures of the [4.2.0] glycopolymers would evoke distinct biological responses; [4.2.0]-cyclohexene glycopolymers induced AE in mouse sperm while [4.2.0]-dioxepin glycopolymers did not. Herein, we provide two options for glycopolymers with low to moderate molecular weight dispersities and low cytotoxicity that can be implemented into biological assays based on the desired hydrophobicity, rigidity, and structural conformation of the polymer probe.
配体-受体相互作用促进了无数的生物过程。这些相互作用的低亲和力通常通过多价结合来增强，以促进结合。然而，每种生物相互作用都需要配体独特的展示和取向。因此，合成多价探针的可用性和多样性对于研究配体-受体结合相互作用非常重要。在此，我们报道了由双环[4.2.0]辛-6-烯-7-甲酰胺与4,7-二氢-1,3-二氧杂环庚烷或环己烯制备的糖聚合物。这些糖聚合物通过交替开环易位聚合合成，显示出精确的配体间距以及疏水性或缩醛官能化聚合物主链的选择。小角X射线散射（SAXS）数据分析表明，这些[4.2.0]糖聚合物在溶液中呈现出不同的构象。在水性介质中，[4.2.0]-二氧杂环庚烷糖聚合物形成具有棒状、柔性结构的肿胀聚合物链，而[4.2.0]-环己烯糖聚合物呈现紧凑的球状结构。为了说明这些糖聚合物如何有助于探索配体-受体相互作用，我们将[4.2.0]糖聚合物纳入生物测定中，以评估它们作为小鼠精子顶体胞吐作用（AE）激活剂的潜力。生物测定结果证实，[4.2.0]糖聚合物的不同结构会引发不同的生物学反应；[4.2.0]-环己烯糖聚合物诱导小鼠精子发生AE，而[4.2.0]-二氧杂环庚烷糖聚合物则不会。在此，我们提供了两种具有低至中等分子量分散度和低细胞毒性的糖聚合物选项，可根据聚合物探针所需的疏水性、刚性和结构构象应用于生物测定中。
