Glycopolymers Prepared by Alternating Ring-Opening Metathesis Polymerization Provide Access to Distinct, Multivalent Structures for the Probing of Biological Activity

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY ACS Bio & Med Chem Au Pub Date : 2024-05-28 DOI:10.1021/acsbiomedchemau.4c0001810.1021/acsbiomedchemau.4c00018
Luz C. Mendez, Francis O. Boadi, Mitchell Kennedy, Surita R. Bhatia and Nicole S. Sampson*, 
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Abstract

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.

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通过交替开环嵌段聚合法制备的含糖聚合物可获得用于生物活性探究的独特多价结构
配体与受体的相互作用促进了无数的生物过程。这些相互作用的亲和力较低,通常通过多价啮合来促进结合。然而,每种生物相互作用都需要配体的独特显示和取向。因此,合成多价探针的可用性和多样性对于配体-受体结合相互作用的研究非常宝贵。在此,我们报告了由双环[4.2.0]辛-6-烯-7-甲酰胺和 4,7-二氢-1,3-二氧杂环庚烷或环己烯制备的聚糖。这些糖聚合物是通过交替开环元合成聚合法合成的,具有精确的配体间距,并可选择疏水或缩醛功能化聚合物骨架。小角 X 射线散射(SAXS)数据分析显示,这些 [4.2.0] 糖聚合物在溶液中具有不同的构象。在水介质中,[4.2.0]-二氧杂环庚烯聚合物形成了具有杆状柔性结构的膨胀聚合物链,而[4.2.0]-环己烯聚合物则具有紧凑的球状结构。为了说明这些聚糖如何有助于探索配体与受体之间的相互作用,我们将[4.2.0]聚糖纳入了一项生物试验,以评估它们作为小鼠精子顶体外渗(AE)激活剂的潜力。生物试验的结果证实,[4.2.0]聚糖的不同结构会引起不同的生物反应;[4.2.0]-环己烯聚糖可诱导小鼠精子的顶体外分泌,而[4.2.0]-二氧杂环庚烷聚糖则不会。在此,我们根据聚合物探针所需的疏水性、刚性和结构构象,提供了两种具有中低分子量分散性和低细胞毒性的糖聚合物选择,可用于生物检测。
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ACS Bio & Med Chem Au
ACS Bio & Med Chem Au 药物、生物、化学-
CiteScore
4.10
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0.00%
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0
期刊介绍: ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.
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