PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 16776512

A class II aldolase mimic.

Jimmy Hedin-Dahlström·Jenny P Rosengren-Holmberg·Sacha Legrand·Susanne Wikman·Ian A Nicholls
View original source ↗Export metadata ↓

Abstract

[structures: see text] A class II aldolase-mimicking synthetic polymer was prepared by the molecular imprinting of a complex of cobalt (II) ion and either (1S,3S,4S)-3-benzoyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (4a) or (1R,3R,4R)-3-benzoyl-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one (4b) in a 4-vinylpyridine-styrene-divinylbenzene copolymer. Evidence for the formation of interactions between the functional monomer and the template was obtained from NMR and VIS titration studies. The polymers imprinted with the template demonstrated enantioselective recognition of the corresponding template structure, and induced a 55-fold enhancement of the rate of reaction of camphor (1) with benzaldehyde (2), relative to the solution reactions, and were also compared to reactions with a series of reference polymers. Substrate chirality was observed to influence reaction rate, and the reaction could be competitively inhibited by dibenzoylmethane (6). Collectively, the results presented provide the first example of the use of enantioselective molecularly imprinted polymers for the catalysis of carbon-carbon bond formation.

Explore related subjects

Aldehyde-LyasesBenzaldehydesCamphorCatalysisChalconesCobaltKetonesKineticsLigandsMolecular StructureOrganometallic CompoundsPolymersStereoisomerismTime FactorsJournal ArticleResearch Support, Non-U.S. Gov't

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Jimmy Hedin-Dahlström, Jenny P Rosengren-Holmberg, Sacha Legrand, Susanne Wikman, Ian A Nicholls. 2006-06-23. A class II aldolase mimic.. https://doi.org/10.1021/jo060608b

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Biochemical and structural exploration of the catalytic capacity of Sulfolobus KDG aldolases.

Aldolases are enzymes with potential applications in biosynthesis, depending on their activity, specificity and stability. In the present study, the genomes of Sulfolobus species were screened for aldolases. Two new KDGA [2-keto-3-deoxygluconate (2-oxo-3-deoxygluconate) aldolases] from Sulfolobus acidocaldarius and Sulfolobus tokodaii were identified, overexpressed in Escherichia coli and characterized. Both enzymes were found to have biochemical properties similar to the previously characterized S. solfataricus KDGA, including the condensation of pyruvate and either D,L-glyceraldehyde or D,L-glyceraldehyde 3-phosphate. The crystal structure of S. acidocaldarius KDGA revealed the presence of a novel phosphate-binding motif that allows the formation of multiple hydrogen-bonding interactions with the acceptor substrate, and enables high activity with glyceraldehyde 3-phosphate. Activity analyses with unnatural substrates revealed that these three KDGAs readily accept aldehydes with two to four carbon atoms, and that even aldoses with five carbon atoms are accepted to some extent. Water-mediated interactions permit binding of substrates in multiple conformations in the spacious hydrophilic binding site, and correlate with the observed broad substrate specificity.

Aldehyde-Lyases↗
PubMed2007

Differential distribution of the lipoxygenase pathway enzymes within potato chloroplasts.

The lipoxygenase pathway is responsible for the production of oxylipins, which are important compounds for plant defence responses. Jasmonic acid, the final product of the allene oxide synthase/allene oxide cyclase branch of the pathway, regulates wound-induced gene expression. In contrast, C6 aliphatic aldehydes produced via an alternative branch catalysed by hydroperoxide lyase, are themselves toxic to pests and pathogens. Current evidence on the subcellular localization of the lipoxygenase pathway is conflicting, and the regulation of metabolic channelling between the two branches of the pathway is largely unknown. It is shown here that while a 13-lipoxygenase (LOX H3), allene oxide synthase and allene oxide cyclase proteins accumulate upon wounding in potato, a second 13-lipoxygenase (LOX H1) and hydroperoxide lyase are present at constant levels in both non-wounded and wounded tissues. Wound-induced accumulation of the jasmonic acid biosynthetic enzymes may thus commit the lipoxygenase pathway to jasmonic acid production in damaged plants. It is shown that all enzymes of the lipoxygenase pathway differentially localize within chloroplasts, and are largely found associated to thylakoid membranes. This differential localization is consistently observed using confocal microscopy of GFP-tagged proteins, chloroplast fractionation, and western blotting, and immunodetection by electron microscopy. While LOX H1 and LOX H3 are localized both in stroma and thylakoids, both allene oxide synthase and hydroperoxide lyase protein localize almost exclusively to thylakoids and are strongly bound to membranes. Allene oxide cyclase is weakly associated with the thylakoid membrane and is also detected in the stroma. Moreover, allene oxide synthase and hydroperoxide lyase are differentially distributed in thylakoids, with hydroperoxide lyase localized almost exclusively to the stromal part, thus closely resembling the localization pattern of LOX H1. It is suggested that, in addition to their differential expression pattern, this segregation underlies the regulation of metabolic fluxes through the alternative branches of the lipoxygenase pathway.

Aldehyde-Lyases↗
PubMed2007

Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via substrate engineering by using "thio-disguised" precursors and oxynitrilase catalysis.

3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2-butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 % ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10) was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute configuration of 5 was verified by crystal structure determination of the corresponding hydrolysis derived carboxylate. The fact that both enzymes yield the same enantiomer was analysed and interpreted by molecular modelling calculations.

Aldehyde-Lyases↗