Expanding the scope of copper artificial metalloenzymes: A potential fluorinase?

IF 3.8 2区 化学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Isabeau Lüddecke, Amanda G. Jarvis
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引用次数: 0

Abstract

Biocatalysts for fluorination are rare, and thus of great interest for artificial enzyme design. Biohybrid catalysts including Cu-based DNAzymes and dinucleotide catalysts can catalyse enantioselective electrophilic fluorination of β-ketoesters. Here we report the investigation of Cu-based artificial metalloenzymes as catalysts for electrophilic fluorination reactions. A library of artificial copper proteins was prepared by bioconjugation of bidentate and tridentate nitrogen ligands to cysteine variants of the Sterol Carrier Protein 2 L (SCP-2 L) and subsequent addition of Cu(II) salts. The resulting copper proteins were screened for activity for the fluorination of β-ketoesters using Selectfluor. Under aqueous acidic conditions it was observed that the designed catalysts did not outcompete the uncatalysed background reaction. This work highlights that careful consideration of substrate reactivity and background reactions is needed when considering potential reactions for artificial metalloenzyme catalysis.

Abstract Image

扩大铜人造金属酶的范围:一种潜在的氟化酶?
用于氟化的生物催化剂很少,因此对人工酶的设计有很大的兴趣。包括铜基DNAzymes和二核苷酸催化剂在内的生物杂化催化剂可以催化β-酮酯的对映选择性亲电氟化。本文报道了铜基人工金属酶作为亲电氟化反应催化剂的研究进展。将双齿和三齿氮配体与甾醇载体蛋白2l (scp - 2l)的半胱氨酸变体进行生物偶联,然后加入Cu(II)盐,制备了人工铜蛋白库。用Selectfluor筛选所得铜蛋白对β-酮酯的氟化活性。在酸性水条件下,所设计的催化剂并不优于未催化的背景反应。这项工作强调,在考虑人工金属酶催化的潜在反应时,需要仔细考虑底物反应性和背景反应。
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来源期刊
Journal of Inorganic Biochemistry
Journal of Inorganic Biochemistry 生物-生化与分子生物学
CiteScore
7.00
自引率
10.30%
发文量
336
审稿时长
41 days
期刊介绍: The Journal of Inorganic Biochemistry is an established international forum for research in all aspects of Biological Inorganic Chemistry. Original papers of a high scientific level are published in the form of Articles (full length papers), Short Communications, Focused Reviews and Bioinorganic Methods. Topics include: the chemistry, structure and function of metalloenzymes; the interaction of inorganic ions and molecules with proteins and nucleic acids; the synthesis and properties of coordination complexes of biological interest including both structural and functional model systems; the function of metal- containing systems in the regulation of gene expression; the role of metals in medicine; the application of spectroscopic methods to determine the structure of metallobiomolecules; the preparation and characterization of metal-based biomaterials; and related systems. The emphasis of the Journal is on the structure and mechanism of action of metallobiomolecules.
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