Janda K D, Lo L C, Lo C H, Sim M M, Wang R, Wong C H, Lerner R A
The Scripps Research Institute, Department of Chemistry, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 1997 Feb 14;275(5302):945-8. doi: 10.1126/science.275.5302.945.
For the past decade the immune system has been exploited as a rich source of de novo catalysts. Catalytic antibodies have been shown to have chemoselectivity, enantioselectivity, large rate accelerations, and even an ability to reroute chemical reactions. In many instances catalysts have been made for reactions for which there are no known natural or man-made enzymes. Yet, the full power of this combinatorial system can only be exploited if there was a system that allows for the direct selection of a particular function. A method that allows for the direct chemical selection for catalysis from antibody libraries was so devised, whereby the positive aspects of hybridoma technology were preserved and re-formatted in the filamentous phage system to allow direct selection of catalysis. This methodology is based on a purely chemical selection process, making it more general than biologically based selection systems because it is not limited to reaction products that perturb cellular machinery.
在过去十年中,免疫系统一直被视作从头催化剂的丰富来源。催化抗体已被证明具有化学选择性、对映选择性、极大的速率加速作用,甚至还具备改变化学反应路径的能力。在许多情况下,人们已经为那些不存在已知天然或人造酶的反应制备了催化剂。然而,只有存在一个能够直接选择特定功能的系统,才能充分利用这个组合系统的全部能力。为此设计了一种允许从抗体库中直接进行化学催化选择的方法,该方法在丝状噬菌体系统中保留并重新构建了杂交瘤技术的积极方面,以实现对催化作用的直接选择。这种方法基于纯粹的化学选择过程,使其比基于生物学的选择系统更具通用性,因为它不限于干扰细胞机制的反应产物。