Department of Chemistry and Biochemistry and California Nanosystems Institute , University of California, Los Angeles , 607 Charles E. Young Drive East , Los Angeles , California 90095-1569 , United States.
Department of Bioengineering , University of California, Los Angeles , 410 Westwood Plaza , Los Angeles , California 90095 , United States.
Bioconjug Chem. 2018 Nov 21;29(11):3739-3745. doi: 10.1021/acs.bioconjchem.8b00635. Epub 2018 Oct 25.
Poly(ethylene glycols) (PEGs) with protein-reactive end-groups are widely utilized in bioconjugation reactions. Herein, we describe the use of ring-opening metathesis polymerization (ROMP) to synthesize unsaturated protein-reactive PEG analogs. These ROMP PEGs (rPEGs) contained terminal aldehyde functionality and ranged in molecular weight from 6 to 20 kDa. The polymers were readily conjugated to free amines on the protein hen egg-white lysozyme (Lyz). Biocompatibility of the unsaturated PEGs was assessed in vitro, revealing the polymers to be nontoxic up to concentrations of at least 1 mg/mL in human dermal fibroblasts (HDFs). The resulting unsaturated rPEG-lysozyme conjugates underwent metathesis-based depolymerization, resulting in decreased molecular weight of the conjugate.
具有蛋白质反应性端基的聚乙二醇（PEGs）广泛应用于生物偶联反应。在此，我们描述了利用开环复分解聚合（ROMP）合成不饱和蛋白质反应性 PEG 类似物。这些 ROMP PEG（rPEG）含有末端醛基官能团，分子量从 6 到 20 kDa 不等。聚合物很容易与蛋白质鸡卵清溶菌酶（Lyz）上的游离伯胺结合。在体外评估了不饱和 PEG 的生物相容性，结果表明聚合物在浓度至少为 1 mg/mL 的情况下对人皮肤成纤维细胞（HDF）是无毒的。所得的不饱和 rPEG-溶菌酶缀合物发生基于复分解的解聚，导致缀合物的分子量降低。
