State Key Laboratory of Fine Chemicals, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518071, China.
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.
J Am Chem Soc. 2024 Aug 28;146(34):24158-24166. doi: 10.1021/jacs.4c08987. Epub 2024 Aug 13.
Cell membrane genetic engineering has been utilized to confer cell membranes with functionalities for diagnostic and therapeutic purposes but concerns over cost and variable modification results. Although nongenetic chemical modification and phospholipid insertion strategies are more convenient, they still face bottlenecks in either biosafety or stability of the modifications. Herein, we show that pyrazolone-bearing molecules can bind to proteins with high stability, which is mainly contributed to by the multiple interactions between pyrazolone and basic amino acids. This new binding model offers a simple and versatile noncovalent approach for cell membrane functionalization. By binding to cell membrane proteins, pyrazolone-bearing dyes enabled precise cell tracking in vitro (>96 h) and in vivo (>21 days) without interfering with the protein function or causing cell death. Furthermore, the convenient anchor of pyrazolone-bearing biotin on cell membranes rendered the biorecognition to avidin, showing the potential for artificially creating cell targetability.
细胞膜基因工程被用于赋予细胞膜用于诊断和治疗目的的功能，但存在成本和可变修饰结果的问题。尽管非遗传化学修饰和磷脂插入策略更方便，但它们在修饰的生物安全性或稳定性方面仍面临瓶颈。在此，我们表明，含有吡唑啉酮的分子可以与蛋白质高度稳定地结合，这主要归因于吡唑啉酮和碱性氨基酸之间的多种相互作用。这种新的结合模型为细胞膜功能化提供了一种简单而通用的非共价方法。通过与细胞膜蛋白结合，含有吡唑啉酮的染料能够在体外（>96 h）和体内（>21 天）进行精确的细胞跟踪，而不会干扰蛋白质功能或导致细胞死亡。此外，细胞膜上含有吡唑啉酮的生物素的方便锚定使得生物素与亲和素的生物识别成为可能，显示了人为创造细胞靶向性的潜力。
