15574-69-3Relevant academic research and scientific papers
BesC Initiates C–C Cleavage through a Substrate-Triggered and Reactive Diferric-Peroxo Intermediate
Chang, Wei-Chen,Guo, Yisong,Makris, Thomas M.,Manley, Olivia M.,Tang, Haoyu,Xue, Shan
supporting information, p. 21416 - 21424 (2021/12/27)
BesC catalyzes the iron- and O2-dependent cleavage of 4-chloro-l-lysine to form 4-chloro-l-allylglycine, formaldehyde, and ammonia. This process is a critical step for a biosynthetic pathway that generates a terminal alkyne amino acid which can be leveraged as a useful bio-orthogonal handle for protein labeling. As a member of an emerging family of diiron enzymes that are typified by their heme oxygenase-like fold and a very similar set of coordinating ligands, recently termed HDOs, BesC performs an unusual type of carbon–carbon cleavage reaction that is a significant departure from reactions catalyzed by canonical dinuclear-iron enzymes. Here, we show that BesC activates O2 in a substrate-gated manner to generate a diferric-peroxo intermediate. Examination of the reactivity of the peroxo intermediate with a series of lysine derivatives demonstrates that BesC initiates this unique reaction trajectory via cleavage of the C4–H bond; this process represents the rate-limiting step in a single turnover reaction. The observed reactivity of BesC represents the first example of a dinuclear-iron enzyme that utilizes a diferric-peroxo intermediate to capably cleave a C–H bond as part of its native function, thus circumventing the formation of a high-valent intermediate more commonly associated with substrate monooxygenations.
METHODS FOR SELECTIVELY MODIFYING AMINO ACIDS AND PRODUCTS MADE THEREBY
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Paragraph 0027; 0123; 0124, (2021/01/29)
Disclosed herein are methods for the selective substitution of a hydrogen bonded to a carbon atom (e.g., a hydrogen of an aliphatic methylene group) of a compound, which comprise contacting the compound with a substituent in the presence of a BesD halogenase.
METHOD FOR PRODUCING cis-5-HYDROXY-2-PIPERIDINECARBOXYLIC ACID DERIVATIVE, AND METHOD FOR PURIFYING cis-5-HYDROXY-2-PIPERIDINECARBOXYLIC ACID
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Paragraph 0158, (2015/07/15)
The present invention aims to provide a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid with high purity, and a method for producing its derivative. The present invention provides a method for producing a cis-5-hydroxy-2-piperidinecarboxylic acid derivative, which method comprises a step of converting cis-5-hydroxy-2-piperidinecarboxylic acid into a compound(s) of Formula (1) and/or Formula (2) (wherein R1 represents a protective group for an amino group, and R2 represents a C1-C6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.
3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation
Morin, Eedicte,Bubb, William A.,Davies, Michael J.,Dean, Roger T.,Fu, Shanlin
, p. 1265 - 1273 (2007/10/03)
γ-Irradiation of several amino acids (Val, Leu, Ile, Lys, Pro, and Glu) in the presence of O2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO°attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3- hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4- hydroxyhexanoic acid], (2S,5R)5-hydroxylysine [(2S,5R)-2,6-diamino-5- hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5- hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9- fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu- Phe) and proteins (BSA and histone H1) exposed to HO°/O2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.
