Glikson M, Arad-Yellin R, Ghozi M, Raveh L, Green B S, Eshhar Z
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Mol Immunol. 1992 Jul-Aug;29(7-8):903-10. doi: 10.1016/0161-5890(92)90128-k.
The production of antibodies against the highly toxic organophosphorus compound soman (GD) has been undertaken. Monoclonal antibodies were raised against two structural analogs of soman which served as haptens for immunization. In these soman analogs the chemically active P-F bond of the soman molecule was substituted by a P-OH group (which is ionized to P-O- under physiological conditions) or a P-H bond, creating compounds which we have named GDOH and GDH, respectively. These soman analogs were linked to carrier proteins through a short linker extending from the pinacolyl group. Monoclonal antibodies were selected according to their ability to bind to the immunizing hapten, and their specificities were determined by competitive inhibition assays. Out of total of 103 anti-GDOH antibodies 22 bound soman, whereas no binding was achieved with 62 anti-GDH antibodies. The two groups of monoclonal antibodies differed also in their structural specificity as demonstrated by different reactivities against a variety of soman analogs and substituted derivatives. These studies indicate that in order to achieve further improvement in anti-soman reactivity with protective potential, other groups (which resemble the OH group) have to be substituted for the F atom in the soman molecule.
已开展针对剧毒有机磷化合物梭曼（GD）的抗体生产工作。针对梭曼的两种结构类似物制备了单克隆抗体，这两种类似物用作免疫的半抗原。在这些梭曼类似物中，梭曼分子具有化学活性的P - F键被P - OH基团（在生理条件下会离子化为P - O⁻）或P - H键取代，从而分别产生了我们命名为GDOH和GDH的化合物。这些梭曼类似物通过从频哪醇基延伸出的短连接子与载体蛋白相连。根据单克隆抗体与免疫半抗原结合的能力进行筛选，并通过竞争性抑制试验确定其特异性。在总共103种抗GDOH抗体中，有22种能与梭曼结合，而62种抗GDH抗体均未实现结合。两组单克隆抗体在结构特异性上也存在差异，这通过它们对多种梭曼类似物和取代衍生物的不同反应性得以证明。这些研究表明，为了在具有保护潜力的抗梭曼反应性方面取得进一步改善，必须用其他基团（类似于OH基团）取代梭曼分子中的F原子。
