Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
Inorg Chem. 2013 Jan 7;52(1):77-83. doi: 10.1021/ic301175f. Epub 2012 Dec 10.
The unique metal abstracting peptide asparagine-cysteine-cysteine (NCC) binds nickel in a square planar 2N:2S geometry and acts as a mimic of the enzyme nickel superoxide dismutase (Ni-SOD). The Ni-NCC tripeptide complex undergoes rapid, site-specific chiral inversion to dld-NCC in the presence of oxygen. Superoxide scavenging activity increases proportionally with the degree of chiral inversion. Characterization of the NCC sequence within longer peptides with absorption, circular dichroism (CD), and magnetic CD (MCD) spectroscopies and mass spectrometry (MS) shows that the geometry of metal coordination is maintained, though the electronic properties of the complex are varied to a small extent because of bis-amide, rather than amine/amide, coordination. In addition, both Ni-tripeptide and Ni-pentapeptide complexes have charges of -2. This study demonstrates that the chiral inversion chemistry does not occur when NCC is embedded in a longer polypeptide sequence. Nonetheless, the superoxide scavenging reactivity of the embedded Ni-NCC module is similar to that of the chirally inverted tripeptide complex, which is consistent with a minor change in the reduction potential for the Ni-pentapeptide complex. Together, this suggests that the charge of the complex could affect the SOD activity as much as a change in the primary coordination sphere. In Ni-NCC and other Ni-SOD mimics, changes in chirality, superoxide scavenging activity, and oxidation of the peptide itself all depend on the presence of dioxygen or its reduced derivatives (e.g., superoxide), and the extent to which each of these distinct reactions occurs is ruled by electronic and steric effects that emenate from the organization of ligands around the metal center.
独特的金属螯合肽天冬酰胺-半胱氨酸-半胱氨酸（NCC）以正方形平面 2N:2S 几何形状结合镍，并作为酶镍超氧化物歧化酶（Ni-SOD）的模拟物。在氧气存在下，Ni-NCC 三肽复合物快速、特异性地发生手性反转，生成 dld-NCC。超氧化物清除活性与手性反转程度成正比增加。通过吸收、圆二色性（CD）和磁圆二色性（MCD）光谱以及质谱（MS）对具有更长肽序列的 NCC 序列进行表征，表明金属配位的几何形状得以保持，尽管由于双酰胺而非胺/酰胺配位，复合物的电子性质在很小程度上发生变化。此外，Ni-三肽和 Ni-五肽复合物都带有-2 个电荷。这项研究表明，当 NCC 嵌入更长的多肽序列中时，手性反转化学不会发生。尽管如此，嵌入的 Ni-NCC 模块的超氧化物清除反应性与手性反转的三肽复合物相似，这与 Ni-五肽复合物的还原电位略有变化一致。综上所述，这表明复合物的电荷可能与配体在金属中心周围的组织所产生的电子和空间效应一样，对 SOD 活性产生影响。在 Ni-NCC 和其他 Ni-SOD 模拟物中，手性、超氧化物清除活性和肽本身的氧化变化都取决于二氧或其还原衍生物（例如超氧化物）的存在，并且这些不同反应发生的程度取决于从配体围绕金属中心的组织中发出的电子和空间效应。
