Lühmann Tessa, Jones Gabriel, Gutmann Marcus, Rybak Jens-Christoph, Nickel Joachim, Rubini Marina, Meinel Lorenz
Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany.
Chair of Tissue Engineering and Regenerative Medicine, University Hospital of Wuerzburg, Roentgenring 11, 97070 Wuerzburg Germany.
ACS Biomater Sci Eng. 2015 Sep 14;1(9):740-746. doi: 10.1021/acsbiomaterials.5b00236. Epub 2015 Aug 5.
Presentation of therapeutic proteins on material surfaces is challenged by random immobilization chemistries through lysine or cysteine residues, typically leading to heterogeneous product outcome. Pharmaceutical quality standards warrant a controlled process ideally through site specific conjugation. Therefore, we deployed genetic codon expansion to engineer a propargyl-l-lysine (Plk)-modified FGF-2 analogue, enabling site-specific copper(I)-catalyzed azide alkyne cycloaddition (CuAAC). Site-specific decoration of Plk-FGF-2 to particles sparked cell proliferation of human osteosarcoma cells in a spatially controlled manner around the decorated carrier, rendering this approach instrumental for the future design of quality-improved bioinstructive scaffold outcome.
通过赖氨酸或半胱氨酸残基进行随机固定化学方法，将治疗性蛋白质呈现在材料表面面临挑战，这通常会导致产物不均一。药品质量标准要求理想情况下通过位点特异性偶联实现可控过程。因此，我们采用遗传密码子扩展技术设计了一种炔丙基-L-赖氨酸（Plk）修饰的FGF-2类似物，实现位点特异性铜（I）催化的叠氮化物-炔烃环加成反应（CuAAC）。将Plk-FGF-2位点特异性修饰到颗粒上，以空间可控的方式在修饰载体周围引发人骨肉瘤细胞的增殖，使这种方法有助于未来设计质量更高的生物指导性支架产物。
