Baskin Maria, Maayan Galia
Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 32000, Israel.
Biopolymers. 2015 Sep;104(5):577-84. doi: 10.1002/bip.22675.
Metal ions play a significant role in the activity of biological systems including catalysis, recognition and folding. Therefore, introducing metal ions into peptidomimetic oligomers is a potential way for creating biomimetic metal complexes toward applications in sensing, recognition, drug design and catalysis. Herein we report the design, synthesis and characterization of water-soluble chiral N-substituted glycine oligomers, "peptoids," with one and two distinct intramolecular binding sites for metal ions such as copper and cobalt. We demonstrate for the first time the incorporation of the chiral hydrophilic group (S)-(+)-1-methoxy-2-propylamine (Nsmp) within peptoid sequences, which provides both chirality and water solubility. Two peptoids, a heptamer, and a dodecamer bearing two and four 8-hydroxyquinoline (HQ) groups respectively as metal-binding ligands, were synthesized on solid support using the submonomer approach. Using UV-titrations and ESI-MS analysis we demonstrate the creation of a novel metallopeptoid bearing two metal ions in distinct binding sites via intramolecular chelation. Exciton couplet circular dichroism (ECCD) demonstrated chiral induction from the chiral non-helical peptoids to the metal centers.
金属离子在包括催化、识别和折叠在内的生物系统活性中发挥着重要作用。因此，将金属离子引入拟肽低聚物是制备用于传感、识别、药物设计和催化的仿生金属配合物的一种潜在方法。在此，我们报道了具有一个和两个用于铜和钴等金属离子的不同分子内结合位点的水溶性手性N-取代甘氨酸低聚物（“类肽”）的设计、合成和表征。我们首次证明了在类肽序列中引入手性亲水基团(S)-(+)-1-甲氧基-2-丙胺(Nsmp)，它既提供了手性又具有水溶性。使用亚单体方法在固相载体上合成了两种类肽，一种七聚体和一种十二聚体，分别带有两个和四个作为金属结合配体的8-羟基喹啉(HQ)基团。通过紫外滴定和电喷雾质谱分析，我们证明了通过分子内螯合在不同结合位点形成了一种新型的含有两个金属离子的金属类肽。激子偶合圆二色性(ECCD)证明了从手性非螺旋类肽到手性金属中心的手性诱导。
