Physico-chemical evaluation of rationally designed melanins as novel nature-inspired radioprotectors.

Physico-chemical evaluation of rationally designed melanins as novel nature-inspired radioprotectors.
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DOI:
10.1371/journal.pone.0007229
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发表时间:
2009-09-30
期刊:
影响因子:
3.7
通讯作者:
Dadachova E
Dadachova E
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Schweitzer AD;Howell RC;Jiang Z;Bryan RA;Gerfen G;Chen CC;Mah D;Cahill S;Casadevall A;Dadachova E

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黑色素是一种高分子量的色素,在自然界中无处不在,可以保护黑色素化的微生物免受高剂量的电离辐射。然而,黑色素与电离辐射相互作用的物理机制尚不清楚。通过元素分析和高效液相色谱分析,我们合理设计了5- s -半胱氨酸- dopa、l-半胱氨酸/L-DOPA、L-DOPA等不同结构的黑色素。含硫黑色素比不含硫黑色素具有更高的预测衰减系数。所有合成黑色素均表现出较强的电子顺磁共振(分别为2.14·1018、7.09·1018和9.05·1017自旋/g),含硫黑色素的光谱更复杂,稳定自由基数量更多。高剂量(30,000 cGy)、高能(137Cs, 661.6 keV)辐照后,稳定自由基的质量和数量均未发生变化,表明其具有较高的自由基稳定性和抗γ辐照电离效应的能力。合理设计的黑色素保护哺乳动物细胞免受不同能量的电离辐射。我们提出,由于黑色素中含有大量的芳香族低聚物,它们含有多π-电子系统,产生的康普顿反冲电子在通过色素时逐渐失去能量,直到能量足够低,可以被色素中存在的稳定自由基所捕获。黑色素控制高能反冲电子的耗散,防止二次电离和产生有害的自由基。
Melanin, a high-molecular weight pigment that is ubiquitous in nature, protects melanized microorganisms against high doses of ionizing radiation. However, the physics of melanin interaction with ionizing radiation is unknown. We rationally designed melanins from either 5-S-cysteinyl-DOPA, L-cysteine/L-DOPA, or L-DOPA with diverse structures as shown by elemental analysis and HPLC. Sulfur-containing melanins had higher predicted attenuation coefficients than non-sulfur-containing melanins. All synthetic melanins displayed strong electron paramagnetic resonance (2.14·1018, 7.09·1018, and 9.05·1017 spins/g, respectively), with sulfur-containing melanins demonstrating more complex spectra and higher numbers of stable free radicals. There was no change in the quality or quantity of the stable free radicals after high-dose (30,000 cGy), high-energy (137Cs, 661.6 keV) irradiation, indicating a high degree of radical stability as well as a robust resistance to the ionizing effects of gamma irradiation. The rationally designed melanins protected mammalian cells against ionizing radiation of different energies. We propose that due to melanin's numerous aromatic oligomers containing multiple π-electron system, a generated Compton recoil electron gradually loses energy while passing through the pigment, until its energy is sufficiently low that it can be trapped by stable free radicals present in the pigment. Controlled dissipation of high-energy recoil electrons by melanin prevents secondary ionizations and the generation of damaging free radical species.
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