Targeting peptides with an iron-based oxidant: Cleavage of the amino acid backbone and oxidation of side chains
Targeting peptides with an iron-based oxidant: Cleavage of the amino acid backbone and oxidation of side chains
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DOI：
10.1021/ja075075i
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发表时间：
2007-10-17
影响因子：
15
通讯作者：
Kodanko, Jeremy J.
中科院分区：
文献类型：
--
作者：
Ekkati, Anil R.;Kodanko, Jeremy J.
描述了使用铁基氧化剂氧化受保护的氨基酸。构建了通式Ac-X-NHTBu的底物，其中X=Gly(1)、Ala(2)、Val(3)、Phe(4)、Tyr(5)、Trp(6)和Met(7)，用于模拟多肽链中的单个氨基酸残基。1在铁催化剂[Fe-II(N4Py)(MeCN)1(ClO4)(2)(8)和KHSO5的作用下氧化，导致氨基酸主链断裂，生成N-乙酰甲酰胺。由8衍生的铁基氧化剂[Fe-IV(O)(N4Py)](2+)在2，2-d(2)-1(96%D)存在下的分解速度比1慢，给出了4.8的动力学同位素效应，这与[FeIv(O)(N4py)](2+)断裂1的α-CH键是一致的。脂肪族氨基酸底物2和3在与1相同的条件下不与[Fe-IV(O)(N4Py)](2+)反应。与底物4-7一起观察到氨基酸侧链的氧化。[FeIv(O)(N4Py)]2+在10当量的I和4-7作用下的分解表明，5对(FeO)-O-IV物种的反应活性最强。[Fe-IV(O)(N4py)](2+)([Fe]=1 mm，1：1H2O/MeCN)经6、7和1分解后的准一级反应速率常数分别为17.0(5)×10(-3)、3.15(8)×10-3和5.8(2)×10(-5)S(-1)。
The oxidation of protected amino acids using an iron-based oxidant is described. Substrates of the general formula Ac-X-NHt Bu, where X = Gly (1), Ala (2), Val (3), Phe (4), Tyr (5), Trp (6), and Met (7) were constructed to model individual amino acid residues within a polypeptide chain. Oxidation of 1 by the iron catalyst [Fe-II(N4Py)(MeCN)1(ClO4)(2) (8) and KHSO5 leads to scission of the amino acid backbone and produces N -acetylformamide as the major product. Decomposition of the iron-based oxidant [Fe-IV(O) (N4Py)](2+), derived from 8, is slower in the presence of 2,2-d (2)-1(96% D) than with 1, giving a kinetic isotope effect of 4.8, which is consistent with [FeIv(O)(N4py)](2+) cleaving an alpha-CH bond of 1. Aliphatic amino acid substrates 2 and 3 do not react with [Fe-IV(O) (N4Py)](2+) under the same conditions used with 1. With substrates 4-7 oxidation of the amino acid side chain is observed. Decomposition of [FeIv(O)(N4Py)]2+ upon treatment with 10 equiv of I and 4-7 revealed that 5 is the most reactive toward the (FeO)-O-IV species. Pseudo-first-order rate constants of 17.0(5) x 10(-3), 3.15(8) x 10-3 and 5.8(2) x 10(-5) s(-1) were obtained for decomposition of [Fe-IV(O)(N4py)](2+) ([Fe] = 1 mM, 1:1 H2O/MeCN) by 6, 7, and 1, respectively.