Aspartyl Oxidation Catalysts That Dial In Functional Group Selectivity, along with Regio- and Stereoselectivity.
Aspartyl Oxidation Catalysts That Dial In Functional Group Selectivity, along with Regio- and Stereoselectivity.
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DOI：
10.1021/acscentsci.6b00237
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发表时间：
2016-10-26
影响因子：
18.2
通讯作者：
Miller, Scott J.
中科院分区：
文献类型：
--
作者：
Alford, Joshua S.;Abascal, Nadia C.;Shugrue, Christopher R.;Colvin, Sean M.;Romney, David K.;Miller, Scott J.
酶进化的一个显著方面是催化机制对于根本不同的化学反应的可移植性。例如，含有两个活性位点羧酸基团的乙酰基蛋白酶催化酰胺键的水解，而通常也含有两个活性位点羧酸根的糖基转移酶（和糖基水解酶）已经进化成形成（或断裂）糖苷键。然而，这两种催化剂在细胞内环境中都没有表现出交叉反应性。这些生物催化剂的大分子结构使其活性位点适应其精确的、不同的功能。真正正交化学反应的小分子催化剂的类似便携性是罕见的。在此，我们报告了含有天冬氨酸的肽，这些肽可以针对底物的不同部分，其中交叉反应性的危险很大。一种瞬时形成的过酸催化剂可作为亲电氧化剂参与催化烯烃环氧化或作为亲核氧化剂参与介导酮的Baeyer-Villiger氧化（BVO）。我们在这项研究中表明，附加的肽序列可以决定这种保守的催化功能基团的反应模式，在一个底物，有可能进行烯烃环氧化和BVO;在这两种情况下，化学选择性（区域和立体选择性）的其他方面是高的。这种序列依赖性调谐的一个共同的催化部分的官能团选择性反应构成了一个仿生策略，可能会影响后期多样化的复杂的多官能分子。乙酰基肽催化剂的顺序可以决定复杂底物内的官能团选择性，其中瞬时过酸充当亲电试剂或亲核试剂，催化正交化学反应。
A remarkable aspect of enzyme evolution is the portability of catalytic mechanisms for fundamentally different chemical reactions. For example, aspartyl proteases, which contain two active site carboxylic acid groups, catalyze the hydrolysis of amide bonds, while glycosyltransferases (and glycosyl hydrolases), which often also contain two active site carboxylates, have evolved to form (or break) glycosidic bonds. However, neither catalyst exhibits cross-reactivity in the intracellular environment. The large, macromolecular architectures of these biocatalysts tailor their active sites to their precise, divergent functions. The analogous portability of a small-molecule catalyst for truly orthogonal chemical reactivity is rare. Herein, we report aspartic acid containing peptides that can be directed to different sectors of a substrate for which the danger of cross-reactivity looms large. A transiently formed aspartyl peracid catalyst can participate either as an electrophilic oxidant to catalyze alkene epoxidation or as a nucleophilic oxidant to mediate the Baeyer–Villiger oxidation (BVO) of ketones. We show in this study that an appended peptide sequence can dictate the mode of reactivity for this conserved catalytic functional group within a substrate that has the potential to undergo both alkene epoxidation and BVO; in both cases the additional aspects of chemical selectivity (regio- and stereoselectivity) are high. This sequence-dependent tuning of a common catalytic moiety for functional group selective reactions constitutes a biomimetic strategy that may impact late-stage diversification of complex polyfunctional molecules. The sequence of an aspartyl peptide catalyst can dictate functional group selectivity within a complex substrate, wherein a transient peracid acts as either an electrophile or a nucleophile, catalyzing orthogonal chemical reactions.
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影响因子：
15
作者：
Peris, Gorka;Jakobsche, Charles E.;Miller, Scott J.
通讯作者：
Miller, Scott J.
影响因子：
4
作者：
TANG, J;WONG, RNS
通讯作者：
WONG, RNS
影响因子：
16.6
作者：
Jakobsche, Charles E.;Peris, Gorka;Miller, Scott J.
通讯作者：
Miller, Scott J.
影响因子：
14.8
作者：
Williamson, James R.
通讯作者：
Williamson, James R.
影响因子：
8.4
作者：
Abascal, Nadia C.;Lichtor, Phillip A.;Miller, Scott J.
通讯作者：
Miller, Scott J.