Gavrilyuk Julia I, Wuellner Ulrich, Barbas Carlos F
The Skaggs Institute for Chemical Biology and the Departments of Molecular Biology and Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1421-4. doi: 10.1016/j.bmcl.2009.01.028. Epub 2009 Jan 15.
Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with beta-lactam-equipped targeting modules. A model study was first performed with beta-lactam conjugated to biotin. This conjugate efficiently and selectively modified the catalytic site lysine (LysH93) of mAb 38C2. We then conjugated a beta-lactam to a cyclic-RGD peptide to chemically program mAb 38C2 to target integrin receptors alpha(v)beta(3) and alpha(v)beta(5). The chemically programmed antibody bound specifically to the isolated integrin receptor proteins as well as the integrins expressed on human melanoma cells. This approach provides an efficient and versatile solution to irreversible chemical programming of aldolase antibodies.
使用配备β-内酰胺的靶向模块实现了单克隆醛缩酶抗体（mAb）38C2的不可逆化学编程。首先进行了一项模型研究，将β-内酰胺与生物素偶联。这种偶联物有效且选择性地修饰了mAb 38C2的催化位点赖氨酸（LysH93）。然后我们将β-内酰胺与环RGD肽偶联，对mAb 38C2进行化学编程，使其靶向整合素受体α(v)β(3)和α(v)β(5)。化学编程后的抗体与分离的整合素受体蛋白以及人黑色素瘤细胞上表达的整合素特异性结合。这种方法为醛缩酶抗体的不可逆化学编程提供了一种高效且通用的解决方案。
