新型含磷抗原的合成

肽键的水解在生命化学中起着重要的作用, 利用人工合成的抗原诱导具备天然肽酶活性的抗体酶具有深远意义, 因而众多的工作集中于催化酰胺键和肽键水解的抗体酶的研究. 这些工作通常是以Paulling的过渡态理论为指导, 以磷为中心原子设计合成类似肽键或酰胺键水解过渡态结构的过渡态类似物. 然而按照这种方法得到的抗体酶很少具有肽酶活性. 金声等1]曾以CPA的肽底物马脲酰苯丙氨酸为模型, 以四面体过渡态类似物为基础, 用硫代替磷, 设计合成了新型半抗原2]. 制备了相应的具有活性的抗体酶, 然而这样的结果尚不能说明以硫原子代替磷原子的方法的优越性, 因此有必要以磷原子为中心原子合成出一个类似抗原, 将其诱导出的抗体相互比较, 才能得到有意义的结论. 本文报道了含磷抗原的合成, 合成路线如下:

Synthesis of a Novel Antigen Containing P

It is of great importance to study the catalytic antibody that catalyzes the hydrolysis of peptide bond. The synthesis of a new kind of antigen(10) containing phosphorus was reported in this paper, which was designed and synthesized according to hippuryl phenylalanine, a substrate of carboxypeptidase A(CPA). To mimic the structure of the substrate, the free C-terminal carboxylic group was remained. However, it was not easy to synthesize the phosphonamide peptide hapten(7) directly, so compound 5 was synthesized firstly, after the catalytic hydrogenolysis it was coupled with p-nitrobenzoyl chloride to get compound(7). The synthesis of antigen and further preparation of antibody will be a good foundation for the activity study of the antibody.