Abebe Adal, Zheng Dong, Evans Jason, Sugumaran Manickam
Department of Biology, University of Massachusetts Boston, Boston, MA 02125, USA.
Department of Chemistry, University of Massachusetts Boston, Boston, MA 02125, USA.
Bioorg Chem. 2016 Jun;66:33-40. doi: 10.1016/j.bioorg.2016.03.006. Epub 2016 Mar 15.
Post-translational modification of peptidyl tyrosine to peptidyl dopa is widely observed in different marine organisms. While peptidyl dopas are oxidatively converted to dehydrodopa derivatives, nothing is known about the further fate of dehydrodopyl compounds. To fill this void, we studied the oxidation chemistry of a peptidyl dehydrodopa mimic, 1,2-dehydro-N-acetyldopa methyl ester with mushroom tyrosinase. We employed both routine biochemical studies and reversed phase liquid chromatography mass spectrometry to investigate the course of the reaction. Tyrosinase catalyzed the oxidation of 1,2-dehydro-N-acetyldopa methyl ester readily generating its typical o-quinone as the transient two-electron oxidation product. This quinone was extremely unstable and rapidly reacted with the parent compound forming benzodioxan type oligomeric products. Reaction mixture containing chemically made o-benzoquinone and 1,2-dehydro-N-acetyldopa methyl ester generated a mixed adduct of benzoquinone and 1,2-dehydro-N-acetyldopa methyl ester. Based on this finding, we propose that peptidyl dehydrodopa also exhibits a similar transformation accounting partially for the adhesive and cementing properties of dopyl proteins in nature.
肽基酪氨酸向肽基多巴的翻译后修饰在不同海洋生物中广泛存在。虽然肽基多巴可被氧化转化为脱氢多巴衍生物，但关于脱氢多巴化合物的进一步去向却一无所知。为填补这一空白，我们研究了肽基脱氢多巴模拟物1,2 - 脱氢 - N - 乙酰多巴甲酯与蘑菇酪氨酸酶的氧化化学。我们采用常规生化研究和反相液相色谱质谱法来研究反应过程。酪氨酸酶催化1,2 - 脱氢 - N - 乙酰多巴甲酯的氧化，很容易生成其典型的邻醌作为瞬时双电子氧化产物。这种醌极不稳定，会迅速与母体化合物反应形成苯并二恶烷型寡聚产物。含有化学合成邻苯醌和1,2 - 脱氢 - N - 乙酰多巴甲酯的反应混合物生成了苯醌与1,2 - 脱氢 - N - 乙酰多巴甲酯的混合加合物。基于这一发现，我们提出肽基脱氢多巴也表现出类似的转化，这部分解释了自然界中多巴蛋白的粘附和胶结特性。
