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Designed Metal-ATCUN Derivatives: Redox- and Non-redox-Based Applications Relevant for Chemistry, Biology, and Medicine
iScience ( IF 4.6 ) Pub Date : 2020-11-10 , DOI: 10.1016/j.isci.2020.101792
Biplab K Maiti 1 , Nidhi Govil 1 , Taraknath Kundu 1 , José J G Moura 2
Affiliation  

The designed “ATCUN” motif (amino-terminal copper and nickel binding site) is a replica of naturally occurring ATCUN site found in many proteins/peptides, and an attractive platform for multiple applications, which include nucleases, proteases, spectroscopic probes, imaging, and small molecule activation. ATCUN motifs are engineered at periphery by conjugation to recombinant proteins, peptides, fluorophores, or recognition domains through chemically or genetically, fulfilling the needs of various biological relevance and a wide range of practical usages. This chemistry has witnessed significant growth over the last few decades and several interesting ATCUN derivatives have been described. The redox role of the ATCUN moieties is also an important aspect to be considered. The redox potential of designed M-ATCUN derivatives is modulated by judicious choice of amino acid (including stereochemistry, charge, and position) that ultimately leads to the catalytic efficiency. In this context, a wide range of M-ATCUN derivatives have been designed purposefully for various redox- and non-redox-based applications, including spectroscopic probes, target-based catalytic metallodrugs, inhibition of amyloid-β toxicity, and telomere shortening, enzyme inactivation, biomolecules stitching or modification, next-generation antibiotic, and small molecule activation.



中文翻译:


设计的金属-ATCUN 衍生物:与化学、生物学和医学相关的氧化还原和非氧化还原应用



设计的“ATCUN”基序(氨基末端铜和镍结合位点)是许多蛋白质/肽中天然存在的 ATCUN 位点的复制品,并且是多种应用的有吸引力的平台,包括核酸酶、蛋白酶、光谱探针、成像、和小分子活化。 ATCUN基序通过化学或遗传方法与重组蛋白、肽、荧光团或识别域缀合,在外围进行工程设计,满足各种生物学相关性和广泛的实际用途的需求。这种化学反应在过去几十年中得到了显着的发展,并且已经描述了几种有趣的 ATCUN 衍生物。 ATCUN 部分的氧化还原作用也是需要考虑的一个重要方面。设计的 M-ATCUN 衍生物的氧化还原电位通过明智地选择氨基酸(包括立体化学、电荷和位置)进行调节,最终提高催化效率。在此背景下,一系列 M-ATCUN 衍生物被专门设计用于各种基于氧化还原和非氧化还原的应用,包括光谱探针、基于靶标的催化金属药物、β-淀粉样蛋白毒性的抑制和端粒缩短、酶失活、生物分子拼接或修饰、下一代抗生素和小分子激活。

更新日期:2020-11-25
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