16626-02-1Relevant articles and documents
Engineering Biofilms for Biocatalysis
Tsoligkas, Andreas N.,Winn, Michael,Bowen, James,Overton, Tim W.,Simmons, Mark J.H.,Goss, Rebecca J.M.
, p. 1391 - 1395 (2011)
Biofilm, friend not foe: Single species biofilms can be engineered to form robust biocatalysts with greater catalytic activity and significantly improved catalytic longevity than purified and immobilised enzymes. We report the engineering, structural analysis and biocatalytic capability of a biofilm that can mediate the conversion of serine and haloindoles to halotryptophans (see scheme).
An expression system for the efficient incorporation of an expanded set of tryptophan analogues
Petrovic, Dejan M.,Leenhouts, Kees,Van Roosmalen, Maarten L.,Broos, Jaap
, p. 1329 - 1336 (2013)
Biosynthetic incorporation of tryptophan (Trp) analogues in recombinant proteins using an E. coli Trp auxotroph expression host is limited to analogues modified with a small substituent like a fluoro atom or a hydroxyl or amine group. We report here the e
PCSK9 ANTAGONIST COMPOUNDS
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Page/Page column 70-72, (2020/01/12)
Disclosed are compounds of Formula I, or a salt thereof: where A, B, D, X, R1, R2 and R8 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.
Directed evolution of the tryptophan synthase β-subunit for stand-alone function recapitulates allosteric activation
Buller, Andrew R.,Brinkmann-Chen, Sabine,Romney, David K.,Herger, Michael,Murciano-Calles, Javier,Arnold, Frances H.
, p. 14599 - 14604 (2015/12/05)
Enzymes in heteromeric, allosterically regulated complexes catalyze a rich array of chemical reactions. Separating the subunits of such complexes, however, often severely attenuates their catalytic activities, because they can no longer be activated by their protein partners. We used directed evolution to explore allosteric regulation as a source of latent catalytic potential using the β-subunit of tryptophan synthase from Pyrococcus furiosus (PfTrpB). As part of its native αββα complex, TrpB efficiently produces tryptophan and tryptophan analogs; activity drops considerably when it is used as a stand-alone catalyst without the α-subunit. Kinetic, spectroscopic, and X-ray crystallographic data show that this lost activity can be recovered by mutations that reproduce the effects of complexation with the α-subunit. The engineered PfTrpB is a powerful platform for production of Trp analogs and for further directed evolution to expand substrate and reaction scope.
Synthesis of tryptophans by alkylation of chiral glycine enolate equivalents with quaternary gramines
Reinfelds, Matiss,Kalinins, Konstantins,Katkevica, Dace,Zemribo, Ronalds,Katkevics, Martins
, p. 5882 - 5885 (2015/11/02)
Quaternary gramines were found to be a suitable source of the 3-methylindole fragment for diastereoselective alkylation. The best yields and stereoselectivity were obtained for the alkylation of a chiral William's morpholinone enolate. Based on this transformation, a general method for the synthesis of enantiopure, indole ring substituted tryptophan derivatives was developed with good overall yields.
Regioselective enzymatic halogenation of substituted tryptophan derivatives using the FAD-dependent halogenase RebH
Frese, Marcel,Guzowska, Paulina H.,Voss, Hauke,Sewald, Norbert
, p. 1270 - 1276 (2014/05/20)
Regioselective methods to establish carbon-halide bonds are still rare, although halogenation is considered as a commonly used methodology for the functionalization of organic compounds. The incorporation of halogen substituents by organic synthesis usually requires hazardous conditions, shows poor regioselectivity and results in the formation of unwanted byproducts. In addition, halogenation by electrophilic aromatic substitution (SEAr) obeys distinct rules depending on electron-withdrawing or -donating groups already present in the aromatic ring. We employed the tryptophan-7-halogenase RebH for regioselective enzymatic halogenation to overcome these limitations. In combination with a tryptophan synthase, an array of C5- and C6-substituted tryptophan derivatives was synthesized and halogenated by RebH. The halogenase is able override these directing effects and halogenates at the electronically unfavored C7-meta-position, even in presence of ortho/para-directing groups. No business as usual: The tryptophan halogenase RebH from Lechevalieria aerocolonigenes is able to halogenate at the electronically unfavored C7-meta-position of C5-substituted tryptophan derivatives, even in presence of deactivating ortho/para-directing groups.
Synthesis of tripeptides containing d-Trp substituted at the indole ring, assessment of opioid receptor binding and in vivo central antinociception
De Marco, Rossella,Bedini, Andrea,Spampinato, Santi,Gentilucci, Luca
supporting information, p. 6861 - 6866 (2014/10/15)
The noncationizable tripeptide Ac-d-Trp-Phe-GlyNH2 was recently proposed as a novel minimal recognition motif for μ-opioid receptor. The introduction of different substituents (methyl, halogens, nitro, etc.) at the indole of d-Trp significantly influenced receptor affinities and resulted in serum stability and in a measurable effect on central antinociception in mice after ip administration.
Precursor-directed fungal generation of novel halogenated chaetoglobosins with more preferable immunosuppressive action
Ge, Hui Ming,Yan, Wei,Guo, Zhi Kai,Luo, Qiong,Feng, Rui,Zang, Le Yun,Shen, Yan,Jiao, Rui Hua,Xu, Qiang,Tan, Ren Xiang
scheme or table, p. 2321 - 2323 (2011/04/18)
Precursor-fed cultivation of endophytic Chaetomium globosum 1C51 afforded nine novel "unnatural" halogenated chaetoglobosins including those with more preferable immunosuppressive activity.
A convenient one-step synthesis of l-aminotryptophans and improved synthesis of 5-fluorotryptophan
Winn, Michael,Roy, Abhijeet Deb,Grueschow, Sabine,Parameswaran, Raj S.,Goss, Rebecca J.M.
body text, p. 4508 - 4510 (2009/04/08)
A one-pot biotransformation for the generation of a series of l-aminotryptophans using a readily prepared protein extract containing tryptophan synthase is reported. The extract exhibits remarkable stability upon freeze-drying, and may be stored and used for long periods after its preparation without significant loss of activity.
The facile synthesis of a series of tryptophan derivatives
Blaser, Georg,Sanderson, John M.,Batsanov, Andrei S.,Howard, Judith A.K.
, p. 2795 - 2798 (2008/09/19)
This study reports a facile method for the synthesis of a variety of 5- and 6-substituted tryptophan derivatives that are difficult to prepare using alternative enzymatic approaches. Acylation of an activated amino acid, derived from serine in situ, is coupled with an enzymatic resolution step to furnish enantiopure analogues bearing a range of electron withdrawing and releasing substituents. Isolation of a dehydroalanine derivative as a by-product from some reactions provides some insights into the likely mechanism of the reaction.
