- Epoxide derivatives of pipecolic acid and proline are inhibitors of pipecolate oxidase
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The cis-4,5-epoxide derivative of L-pipecolic acid (2S,4S,5R-epoxypipecolic acid, cis-3) was synthesized and found to serve as an excellent substrate for L-pipecolate oxidase (L-PO) and also to cause time-dependent, irreversible inactivation of the enzyme. Data are presented showing this compound is a mechanism-based inhibitor of L-PO, whereas 2S,3R,4S-epoxyproline acts as a reversible inhibitor.
- Ho, Bin,Zabriskie, T. Mark
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- Discovery of New Fe(II)/α-Ketoglutarate-Dependent Dioxygenases for Oxidation of l-Proline
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Genome mining for novel Fe(II)/α-ketoglutarate-dependent dioxygenases (αKGDs) to expand the enzymatic repertoire in the oxidation of l-proline is reported. Through clustering of proteins, we predicted regio- and stereoselectivity in the hydroxylation reaction and validated this hypothesis experimentally. Two novel byproducts in the reactions with enzymes from Bacillus cereus and Streptomyces sp. were isolated, and the structures were determined to be a 3,4-epoxide and a 3,4-diol, respectively. The mechanism for the formation of the epoxide was investigated by performing an 18O-labeling experiment. We propose that the mechanism proceeds via initial cis-3-hydroxylation followed by ring closure. A biocatalytic step was run on subgram quantities of starting material without any significant optimization of the conditions. However, the substrate concentration was 40-fold higher than the usual reported titers for recombinant P450-mediated hydroxylations, showing the synthetic potential of αKGDs on a preparative scale.
- Dussauge, Solene,Moore, Charles,Snajdrova, Radka,Tassano, Erika,Vargas, Alexandra
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supporting information
(2022/02/09)
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- Development of novel cyclic peptides as pro-apoptotic agents
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Our recent finding that paclitaxel behaves as a peptidomimetic of the endogenous protein Nur77 inspired the design of two peptides (PEP1 and PEP2) reproducing the effects of paclitaxel on Bcl-2 and tubulin, proving the peptidomimetic nature of paclitaxel.
- Brindisi, Margherita,Maramai, Samuele,Brogi, Simone,Fanigliulo, Emanuela,Butini, Stefania,Guarino, Egeria,Casagni, Alice,Lamponi, Stefania,Bonechi, Claudia,Nathwani, Seema M.,Finetti, Federica,Ragonese, Francesco,Arcidiacono, Paola,Campiglia, Pietro,Valenti, Salvatore,Novellino, Ettore,Spaccapelo, Roberta,Morbidelli, Lucia,Zisterer, Daniela M.,Williams, Clive D.,Donati, Alessandro,Baldari, Cosima,Campiani, Giuseppe,Ulivieri, Cristina,Gemma, Sandra
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p. 301 - 320
(2016/05/11)
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