Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California 90095, United States.
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California 90095, United States.
Bioconjug Chem. 2024 Jun 19;35(6):744-749. doi: 10.1021/acs.bioconjchem.4c00202. Epub 2024 May 29.
Bioconjugation of polymers to proteins is a method to impart improved stability and pharmacokinetic properties to biologic systems. However, the precise effects of polymer architecture on the resulting bioconjugates are not well understood. Particularly, cyclic polymers are known to possess unique features such as a decreased hydrodynamic radius when compared to their linear counterparts of the same molecular weight, but have not yet been studied. Here, we report the first bioconjugation of a cyclic polymer, poly(ethylene glycol) (PEG), to a model protein, T4 lysozyme, containing a single engineered cysteine residue (V131C). We compare the stability and activity of this conjugate with those of a linear PEG-T4 lysozyme analogue of similar molecular weight. Furthermore, we used molecular dynamics (MD) simulations to determine the behavior of the polymer-protein conjugates in solution. We introduce cyclic polymer-protein conjugates as potential candidates for the improvement of biologic therapeutics.
聚合物与蛋白质的偶联是一种赋予生物系统改善的稳定性和药代动力学性质的方法。然而，聚合物结构对所得生物缀合物的确切影响还不是很清楚。特别是，与相同分子量的线性对应物相比，环状聚合物具有独特的特征，例如水动力半径减小，但尚未得到研究。在这里，我们报告了第一个环状聚合物聚乙二醇（PEG）与模型蛋白 T4 溶菌酶的偶联，该蛋白含有一个单一的工程半胱氨酸残基（V131C）。我们将该缀合物的稳定性和活性与具有相似分子量的线性 PEG-T4 溶菌酶类似物进行了比较。此外，我们使用分子动力学（MD）模拟来确定聚合物-蛋白质缀合物在溶液中的行为。我们将环状聚合物-蛋白质缀合物作为改善生物治疗药物的潜在候选物。
