Sequence-specific peptide cleavage catalyzed by an antibody.
Sequence-specific peptide cleavage catalyzed by an antibody.
复制标题
由抗体催化的序列特异性肽切割。
作者：
Brent L. Iverson;R. Lerner
已经诱导出能够在中性pH下与金属络合物辅因子催化多肽底物Gly-Phe键的特异性水解性的单抗。抗体由Co(III)-三乙烯四胺(Trien)-多肽半抗原免疫制备。这些抗体作为一个组不仅能够与Co(III)的Trien络合物结合，而且能够与许多其他金属的Trien络合物结合。以六种多肽为底物，分别与抗体和各种金属络合物进行比较。这些多肽中的两个被几种抗体切割。对一种抗体进行了详细的研究，并观察到以锌(II)、镓(III)、铁(III)、铟(III)、铜(II)、镍(II)、卢(III)、镁(II)或锰(II)为辅因子的底物被切割。观察到这些衬底的周转数为每秒6×10(-4)。这些结果证明了在抗体结合部位使用辅因子辅助催化来完成困难的化学转化是可行的。
Monoclonal antibodies have been induced that are capable of catalyzing specific hydrolysis of the Gly-Phe bond of peptide substrates at neutral pH with a metal complex cofactor. The antibodies were produced by immunizing with a Co(III) triethylenetetramine (trien)-peptide hapten. These antibodies as a group are capable of binding trien complexes of not only Co(III) but also of numerous other metals. Six peptides were examined as possible substrates with the antibodies and various metal complexes. Two of these peptides were cleaved by several of the antibodies. One antibody was studied in detail, and cleavage was observed for the substrates with the trien complexes of Zn(II), Ga(III), Fe(III), In(III), Cu(II), Ni(II), Lu(III), Mg(II), or Mn(II) as cofactors. A turnover number of 6 x 10(-4) per second was observed for these substrates. These results demonstrate the feasibility of the use of cofactor-assisted catalysis in an antibody binding site to accomplish difficult chemical transformations.