ALPHA,BETA-DEHYDRO-3,4-DIHYDROXYPHENYLALANINE DERIVATIVES - RATE AND MECHANISM OF FORMATION
ALPHA,BETA-DEHYDRO-3,4-DIHYDROXYPHENYLALANINE DERIVATIVES - RATE AND MECHANISM OF FORMATION
复制标题
DOI：
10.1016/0003-9861(91)90324-c
复制
发表时间：
1991-02-15
影响因子：
3.9
通讯作者：
WAITE, JH
中科院分区：
文献类型：
--
作者：
RZEPECKI, LM;WAITE, JH
氨基酸-3，4-二羟基苯丙氨酸(DOPA)，当存在于蛋白质的初级序列中时，不会在氧化为苯二酚时形成黑色素，因为它的胺部分参与了多肽键，不能进行内部环化。取而代之的是，肽基多巴对苯二酚可用于其他反应。我们研究了一种小分子多巴类似物N-乙酰多巴乙酯的氧化化学，结果表明，氧化的主要产物是多巴的不饱和衍生物N-乙酰-α，β-脱氢多巴乙酯(N-乙酰基-Δ-DEE)(见配文，Rzepeckiet al.，Arch)。生物化学。生物群落。(1991)285，17-26。在本研究中，我们探索了NAc-DEE转化为NAc-Δ-DIE的动力学和机理特征，发现该反应需要：(I)NAcDEE氧化成苯二酚，(Ii)以Lewis碱为催化剂(在pH6.0-8.0时，磷酸阴离子是最好的)，以及(Iii)防止竞争反应，如Michael加成反应。在有Lewis碱存在的情况下，pH 8.0时的转化率为12%至19%，pH为6.0时的转化率为35%至90%。至少需要两个独立的反应机理来解释动力学数据：(I)在pH 6.0及以上时的准一级反应机理，以及(Ii)在较高pH时的另一个二级反应机理，它涉及NAcDEE邻苯二酚和苯二酚。在0.1M磷酸二氢钠溶液中，表观拟一级反应速率常数随pH从2.36×10−4S−1增大到约30×10−4S−1。因此，DOPA对苯二酚向脱氢DOPA的互变异构化可能是含有DOPA蛋白质的天然结构硬化的一个因素。
The amino acidl-3,4-dihydroxyphenylalanine (DOPA), when present in the primary sequence of proteins, does not form melanin upon oxidation to the quinone, since its amine moiety participates in a peptide bond and cannot undergo internal cyclization. Instead, peptidyl DOPA quinone is available for other reactions. We have investigated the oxidation chemistry of a low molecular weight peptidyl DOPA analog,N-acetylDOPA ethyl ester (NAcDEE), and have shown that a major product of oxidation is an unsaturated DOPA derivative,N-acetyl-α,β-dehydroDOPA ethyl ester (NAcΔDEE) (see companion paper, Rzepeckiet al., Arch. Biochem. Biophys. (1991) 285, 17–26. In the present study, we have explored kinetic and mechanistic features of the conversion of NAcDEE to NAcΔDEE and found that the reaction requires: (i) oxidation of NAcDEE to the quinone, (ii) the presence of a Lewis base as a catalyst (phosphate anion was the best of those tried in the pH range 6.0–8.0), and (iii) prevention of competing reactions such as Michael additions. Conversion efficiencies in the presence of Lewis bases ranged between 12 and 19% at pH 8.0 and 35 and 90% at pH 6.0. At least two separate reaction mechanisms appeared necessary to explain the kinetic data: (i) a pseudo-first-order mechanism at pH 6.0 and above, and (ii) an additional second-order mechanism at higher pH which involved both NAcDEE catechol and quinone. The apparent pseudo-first-order rate constants increased with pH from 2.36 × 10−4s−1at pH 6.0 to about 30 × 10−4s−1at pH 8.0 in 0.1msodium phosphate. Tautomerization of DOPA quinone to dehydroDOPA may thus be a factor in the sclerotization of natural structures incorporating DOPA containing proteins.