揭示新型黑色素生成途径:通过固态氧化黑色素生物合成前体 5,6-二羟基吲哚,通过自由基-自由基耦合形成意想不到的联苯型二聚体。

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Bioorganic Chemistry Pub Date : 2024-12-01 Epub Date: 2024-10-29 DOI:10.1016/j.bioorg.2024.107928
Sara Viggiano, Maria Laura Alfieri, Lucia Panzella, Orlando Crescenzi, Alessandra Napolitano
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引用次数: 0

摘要

5,6-二羟基吲哚(DHI)是棕黑色皮肤和毛发黑色素的主要生物合成前体之一,对其氧化途径的研究是阐明这些色素在生物系统中结构的一种很有前景的方法。我们在本文中报告了在迄今为止研究较少的条件(即固态机械化学条件)下对 DHI 氧化化学反应的探索,这些条件模仿了体内黑色素体中的条件,黑色素在固态蛋白质基质上的密闭空间中生长,因此可以分离和鉴定新的二聚体。机理实验证明,在固态条件下,自由基-自由基耦合是防止 5,6-二羟基吲哚系统离子聚合的主要二聚体生成途径,这表明这种黑色素生成前体的氧化化学反应在很大程度上取决于反应环境。本文所揭示的 DHI 氧化途径与黑色素生成的相关性还通过在蛋白质存在下进行固态反应的特别实验得到了证明。最后,研究人员还对新二聚体氧化产生的色团进行了调查,以期扩大对黑色素功能特性的了解,其中主要包括光保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disclosing novel melanogenesis pathways: Formation of unexpected biphenyl-type dimers through radical-radical coupling by solid-state oxidation of the melanin biosynthetic precursor 5,6-dihydroxyindole.

Investigation of the oxidation pathway of 5,6-dihydroxyindole (DHI), one of the main biosynthetic precursors of the brown-to-black skin and hair melanin pigments, represents a promising approach for the elucidation of the structure of these pigments in biological systems. We report herein the exploration of DHI oxidation chemistry under conditions so far poorly investigated, i.e. solid-state mechanochemical conditions, mimicking those that could be found in vivo in melanosomes, where melanin growth takes place in a confined space on a solid proteinaceous matrix, that allowed for the isolation and characterization of new dimers. Mechanistic experiments allowed to propose radical-radical coupling as the main dimerization pathway under solid-state conditions preventing ionic polymerization of the 5,6-dihydroxyindole system, indicating that the oxidation chemistry of this melanogenic precursor strongly depends on the reaction environment. The relevance for melanogenesis of the DHI oxidation pathway, disclosed herein, was also demonstrated by ad hoc experiments in which the solid-state reaction was carried out in the presence of proteins. Finally, the chromophores of the species generated by oxidation of the new dimers were investigated with a view to expanding the knowledge on the functional properties of melanin pigments, including mainly photoprotection.

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来源期刊
Bioorganic Chemistry
Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
9.70
自引率
3.90%
发文量
679
审稿时长
31 days
期刊介绍: Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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