Selenomelanin: An Abiotic Selenium Analogue of Pheomelanin
Selenomelanin: An Abiotic Selenium Analogue of Pheomelanin
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DOI：
10.1021/jacs.0c05573
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发表时间：
2020-07-22
影响因子：
15
通讯作者：
Gianneschi, Nathan C.
中科院分区：
文献类型：
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作者：
Cao, Wei;McCallum, Naneki C.;Gianneschi, Nathan C.
黑色素是一种异质生物聚合物家族，普遍存在于植物、动物、细菌和真菌领域，在这些领域它们作为色素和辐射防护剂发挥着各种作用。黑色素有五种多功能，但在结构和生物合成上都不完全了解：真黑色素、神经黑色素、脓黑素、异黑素和现象黑素。尽管到目前为止，真黑素和异黑素一直是大多数辐射防护研究的焦点，但一些研究表明，黑色素对x射线的吸收系数比真黑素更好。我们推断，如果存在富硒黑色素，它将是比含硫黑色素更好的x射线保护器，因为x射线吸收系数与原子序数(Z)的四次方成正比。值得注意的是，硒是一种必需的微量营养素，氨基酸硒半胱氨酸被遗传编码在25种天然人类蛋白质中。因此，我们假设硒黑素存在于自然界中，与已知的黑色素相比，它为生物体提供了更好的电离辐射保护。本文以硒半胱氨酸为原料，通过化学和生物合成途径，介绍了这种新型的硒类黑色素。由此产生的硒黑素是一种类似于现象黑素的结构。我们发现硒黑素在高剂量x射线照射下有效地阻止新生儿人表皮角质形成细胞（NHEK） G2/M期阻滞。令人兴奋的是，硒黑素的这种有益作用表明它是尚未发现的第六种天然黑色素。
Melanins are a family of heterogeneous biopolymers found ubiquitously across plant, animal, bacterial, and fungal kingdoms where they act variously as pigments and as radiation protection agents. There exist five multifunctional yet structurally and biosynthetically incompletely understood varieties of melanin: eumelanin, neuromelanin, pyomelanin, allomelanin, and pheomelanin. Although eumelanin and allomelanin have been the focus of most radiation protection studies to date, some research suggests that pheomelanin has a better absorption coefficient for X-rays than eumelanin. We reasoned that if a selenium enriched melanin existed, it would be a better X-ray protector than the sulfur-containing pheomelanin because the X-ray absorption coefficient is proportional to the fourth power of the atomic number (Z). Notably, selenium is an essential micronutrient, with the amino acid selenocysteine being genetically encoded in 25 natural human proteins. Therefore, we hypothesize that selenomelanin exists in nature, where it provides superior ionizing radiation protection to organisms compared to known melanins. Here we introduce this novel selenium analogue of pheomelanin through chemical and biosynthetic routes using selenocystine as a feedstock. The resulting selenomelanin is a structural mimic of pheomelanin. We found selenomelanin effectively prevented neonatal human epidermal keratinocytes (NHEK) from G2/M phase arrest under high-dose X-ray irradiation. Provocatively, this beneficial role of selenomelanin points to it as a sixth variety of yet to be discovered natural melanin.