Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry. Ruder Boskovic Institute, Zagreb, Croatia.
Pliva Croatia Ltd, Research and Development, Zagreb, Croatia.
Curr Protein Pept Sci. 2019;20(11):1040-1045. doi: 10.2174/1389203720666190513084102.
Small molecule spectrophotometric probes for DNA/RNA and proteins are of the utmost importance for diagnostics in biochemical and biomedical research. Both, naturally occurring and synthetic probes, often include peptide sequence responsible for the selectivity toward the particular target; however, commercially available dyes are restricted to single point attachment to the peptide (having one reactive group). Here presented are our recent advances in the development of novel amino acidfluorophore probes, with the unique characteristic of free N- and C-terminus available for incorporation at any peptide backbone position. Intriguingly, already monomeric amino acid-fluorophores showed recognition among various DNA/RNA, whereby steric impact and contribution of halogens is systematically studied. Moreover, some dyes revealed intracellular mitochondria specificity. Further, several hetero-dimeric chromophore systems were prepared, demonstrating that synergistic effect can lead to simultaneous DNA, RNA and protein fluorimetric recognition, combined with enzyme inhibition. Also, homodimeric cyanines equipped with chlorine revealed intriguing DNA/RNA selectivity in respect to well-known parent TOTO and YOYO dyes.
小分子分光光度探针对于 DNA/RNA 和蛋白质的诊断在生物化学和生物医学研究中至关重要。无论是天然存在的还是合成的探针，通常都包含负责对特定靶标具有选择性的肽序列；然而，商业上可获得的染料仅限于单点连接到肽（具有一个反应基团）。本文介绍了我们在开发新型氨基酸荧光探针方面的最新进展，这些探针具有独特的特点，即 N-端和 C-端均为游离，可在任何肽骨架位置进行结合。有趣的是，已经有单体氨基酸荧光团显示出对各种 DNA/RNA 的识别能力，其中系统地研究了立体影响和卤素的贡献。此外，一些染料显示出对细胞内线粒体的特异性。此外，还制备了几种杂二聚体生色团系统，证明协同效应可以导致同时对 DNA、RNA 和蛋白质进行荧光识别，并结合酶抑制。此外，带有氯的同二聚氰染料显示出与知名的 TOTO 和 YOYO 染料相比，对 DNA/RNA 具有有趣的选择性。
