Univ. Grenoble Alpes, CNRS, CEA, BIG, LCBM (UMR 5249), 38000 Grenoble, France.
Org Biomol Chem. 2018 Aug 8;16(31):5626-5634. doi: 10.1039/c8ob01044g.
Copper(i) is a soft metal ion that plays an essential role in living organisms and Cu+-responsive probes are required to detect Cu+ ions in physiological conditions and understand its homeostasis as well as the diseases associated with its misregulation. In this article, we describe a series of cyclic peptides, which are structurally related to the copper chaperone CusF, and that behave as Cu+-repsonsive probes. These peptide probes comprise the 16-amino acid loop of CusF cyclized by a β-turn inducer dipeptide and functionalized by a Tb3+ complex for its luminescence properties. The mechanism of luminescence enhancement relies on the modulation of the antenna effect between a tryptophan residue and the Tb3+ ion within the probe when Cu+ forms a cation-π interaction with the tryptophan. Here, we investigate the influence of the amino acid sequence of these cyclic peptides on the copper-induced modulation of Tb3+ emission and show that the rigid β-turn inducer Aib-d-Pro and insertion of the Tb3+ complex close to its tryptophan antenna are required to obtain turn-on Cu+ responsive probes. We also show that the amino acid sequence, especially the number and position of proline residues has a significant impact on metal-induced luminescence enhancement and metal-binding constant of the probes.
铜（I）是一种软金属离子，在生物体内发挥着重要作用，需要 Cu+响应探针来检测生理条件下的 Cu+离子，以了解其体内平衡以及与 Cu+失调相关的疾病。在本文中，我们描述了一系列环状肽，它们与铜伴侣蛋白 CusF 在结构上相关，并且可以作为 Cu+响应探针。这些肽探针由 CusF 的 16 个氨基酸环组成，通过β-转角诱导二肽环化，并通过 Tb3+络合物官能化以获得其发光性质。发光增强的机制依赖于当 Cu+与色氨酸形成阳离子-π相互作用时，探针内色氨酸与 Tb3+离子之间的天线效应的调制。在这里，我们研究了这些环状肽的氨基酸序列对铜诱导的 Tb3+发射调制的影响，并表明刚性β-转角诱导剂 Aib-d-Pro 和将 Tb3+络合物插入靠近其色氨酸天线的位置对于获得开启型 Cu+响应探针是必需的。我们还表明，氨基酸序列，特别是脯氨酸残基的数量和位置对探针的金属诱导发光增强和金属结合常数有显著影响。
