Katz B A, Stroud R M, Collins N, Liu B, Arze R
Arris Pharmaceutical Corporation, South San Francisco, CA 94080, USA.
Chem Biol. 1995 Sep;2(9):591-600. doi: 10.1016/1074-5521(95)90123-x.
The cyclic, disulfide-containing peptide, cyclo-Ac-[Cys-His-Pro-Gln-Gly-Pro-Pro-Cys]-NH2, binds to streptavidin with high affinity. In streptavidin-peptide cocrystals of space group I222, cyclic peptide monomers are bound on adjacent streptavidin tetramers related by a crystallographic two-fold symmetry axis. We set out to determine whether the disulfide bonds of the peptide, presented close to one another in the crystal, could undergo disulfide interchange to form a dimer.
When juxtaposed, the disulfides of neighboring peptides undergo disulfide interchange, breaking and forming covalent disulfide bonds, to produce a peptide dimer adopting the symmetry of the crystal. This is the first example of a chemical transformation mediated by a protein crystal lattice. The structure of the streptavidin-bound monomer, and that of the dimer that was eventually produced from it in the crystal, were both determined from the same single crystal studied at different times. The two-fold symmetric peptide dimer was independently synthesized and shown to form crystals of dimerized streptavidin.
We have shown that formation of a covalently linked peptide dimer can be mediated by a protein crystal lattice. The dimer thus produced dimerizes its target, streptavidin, suggesting that solid-state (or topochemical) reactions of this kind may be broadly useful for the preparation of ligands that can dimerize other protein targets.
环状含二硫键肽环 - Ac - [Cys - His - Pro - Gln - Gly - Pro - Pro - Cys] - NH₂与抗生物素蛋白具有高亲和力。在空间群为I222的抗生物素蛋白 - 肽共晶体中，环状肽单体通过晶体学二重对称轴与相邻的抗生物素蛋白四聚体结合。我们着手确定在晶体中彼此靠近呈现的肽的二硫键是否会发生二硫键交换形成二聚体。
当相邻时，相邻肽的二硫键发生二硫键交换，断裂并形成共价二硫键，产生具有晶体对称性的肽二聚体。这是蛋白质晶格介导的化学转化的首个实例。抗生物素蛋白结合的单体结构以及最终在晶体中由其产生的二聚体结构均从不同时间研究的同一单晶中确定。独立合成了具有二重对称性的肽二聚体，并显示其形成二聚化抗生物素蛋白的晶体。
我们已表明共价连接的肽二聚体的形成可由蛋白质晶格介导。由此产生的二聚体使其靶标抗生物素蛋白二聚化，这表明这种固态（或拓扑化学）反应可能广泛用于制备可使其他蛋白质靶标二聚化的配体。
