Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biocatalytic processes were used to prepare chiral intermediates for pharmaceuticals. These include the following processes. Enzymatic synthesis of [4S-(4a,7a,10ab)]1-octahydro-5-oxo-4-[[(phenylmethoxy) carbonyl]amino]-7H-pyrido-[2,1-b] [1,3]thiazepine-7-carboxylic acid methyl ester (BMS-199541-01), a key chiral intermediate for synthesis of a new vasopeptidase inhibitor. Enzymatic oxidation of the epsilon-amino group of lysine in dipeptide dimer N2-[N[[(phenylmethoxy)carbonyl] L-homocysteinyl] L-lysine)1,1-disulfide (BMS-201391-01) to produce BMS-199541-01 using a novel L-lysine epsilon-aminotransferase from S. paucimobilis SC16113 was demonstrated. This enzyme was overexpressed in E. coli, and a process was developed using recombinant enzyme. The aminotransferase reaction required alpha-ketoglutarate as the amine acceptor. Glutamate formed during this reaction was recycled back to alpha-ketoglutarate by glutamate oxidase from S. noursei SC6007. Synthesis and enzymatic conversion of 2-keto-6-hydroxyhexanoic acid 5 to L-6-hydroxy norleucine 4 was demonstrated by reductive amination using beef liver glutamate dehydrogenase. To avoid the lengthy chemical synthesis of ketoacid 5, a second route was developed to prepare the ketoacid by treatment of racemic 6-hydroxy norleucine (readily available from hydrolysis of 5-(4-hydroxybutyl) hydantoin, 6) with D-amino acid oxidase from porcine kidney or T. variabilis followed by reductive amination to convert the mixture to L-6-hydroxynorleucine in 98% yield and 99% enantiomeric excess. Enzymatic synthesis of (S)-2-amino-5-(1,3-dioxolan-2-yl)-pentanoic acid (allysine ethylene acetal, 7), one of three building blocks used for synthesis of a vasopeptidase inhibitor, was demonstrated using phenylalanine dehydrogenase from T. intermedius. The reaction requires ammonia and NADH. NAD produced during the reaction was recycled to NADH by oxidation of formate to CO2 using formate dehydrogenase. Efficient synthesis of chiral intermediates required for total chemical synthesis of a beta 3 receptor agonist was demonstrated. These include: (a) microbial reduction of 4-benzyloxy-3-methanesulfonylamino-2'-bromoacetophenone 9 to corresponding (R)-alcohol 10 by S. paucimobilis SC16113, (b) enzymatic resolution of racemic alpha-methyl phenylalanine amide 11 and alpha-methyl-4-hydroxyphenylalanine amide 13 by amidase from M. neoaurum ATCC 25795 to prepare corresponding (S)-amino acids 12 and 14, and (c) asymmetric hydrolysis of methyl-(4-methoxyphenyl)-propanedioic acid ethyl diester 15 to corresponding (S)-monoester 16 by pig liver esterase. (S)[1-(acetoxyl)-4-(3-phenyl)butyl]phosphonic acid diethyl ester 21, a key chiral intermediate required for total chemical synthesis of BMS-188494 (an anticholesterol drug) was prepared by stereoselective acetylation of racemic [1-(hydroxy)-4-(3-phenyl)butyl]phosphonic acid diethyl ester 22 using G. candidum lipase. Lipase-catalyzed stereoselective acetylation of racemic 7-[N,N'-bis-(benzyloxy-carbonyl)N-(guanidinoheptanoyl)]-alpha-hydroxy-glycine 24 to corresponding S-(-)-acetate 25 was demonstrated. S-(-)-acetate 25 is a key intermediate for total chemical synthesis of (-)-15-deoxyspergualin 23, an immunosuppressive agent and antitumor antibiotic. Stereoselective microbial reduction of (1S)[3-chloro-2-oxo-1-(phenyl-methyl)propyl] carbamic acid, 1,1-dimethyl-ethyl ester 26 to corresponding chiral alcohol 27a (a key chiral intermediate for HIV protease inhibitors) was also demonstrated. Stereospecific enzymatic hydrolysis of racemic epoxide RS-1-[2',3'-dihydro benzo[b]furan-4'-yl]-1,2-oxirane 29 the corresponding R-diol 30 and unreacted chiral S-epoxide 28 was demonstrated using R. glutinis and A. niger. Dynamic resolution of racemic diol RS-1-[2',3'-dihydrobenzo[b]furan-4'-yl]-ethane-1,2-diol 32 to corresponding S-diol S-1-[2',3'-dihydrobenzo[b]furan-4'-yl]-ethane-1,2-diol 31 was demonstrated using C. boidinii and P. methanolica. Chiral (S)-epoxide 28 and (S)-diol 31 are key intermediates for a new prospective circadian modulator drug. Enzymatic resolution of racemic 2-pentanol and 2-heptanol by lipase B from Candida antarctica was demonstrated. S-(+)-2-pentanol is a key chiral intermediate required for synthesis of anti-Alzheimer's drugs.
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PMID:Microbial/enzymatic synthesis of chiral drug intermediates. 1287 94

The development of a new chromatographic reactor based on immobilized Candida rugosa lipase (CRL) is described. The chromatographic system has been used to evaluate the rate differences by which the product enantiomers of esterolytic reactions catalyzed by immobilized CRL are obtained. The method has been applied to a series of racemic 2-aryloxyalkanoic acids and isosteric analogous methyl esters and to some non-steroidal antiinflammatory drugs 2-arylpropanoic acids methyl esters in order to study the structure effects on reaction rate and enantioselectivity. Lipase from C. rugosa has been non-covalently and covalently immobilized on HPLC chromatographic silica supports to develop an immobilized enzyme reactor (IMER). The reactor was connected through a switching valve to an analytical reversed-phase column, which was used for the on-line determination of the hydrolysis rate by peak area integration. The enantiomeric excess of the hydrolytic reaction products was determined off-line on a CSP utilizing immobilized penicillin G acylase (PGA-CSP).
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PMID:Lipases for biocatalysis: development of a chromatographic bioreactor. 1289 62

Recently the potential of enzymes for surface hydrophilisation and/or functionalisation of polyethyleneterephthalate (PET) and polyamide (PA) has been discovered. However, there was no correlation between enzyme class/activity (e.g. esterase, lipase, cutinase) and surface hydrolysis of these polymers and consequently no simple assay to estimate this capability. Enzymes active on the model substrates bis (benzoyloxyethyl) terephthalate and adipic acid bishexyl-amide, were also capable of increasing the hydrophilicity of PET and PA. When dosed at the identical activity on 4-nitrophenyl butyrate, only enzymes from Thermobifida fusca, Aspergillus sp., Beauveria sp. and commercial enzymes (TEXAZYME PES sp5 and Lipase PS) increased the hydrophilicity of PET fibres while other esterases and lipases did not show any effect. Activity on PET correlated with the activity on the model substrate. Hydrophilicity of fibres was greatly improved based on increases in rising height of up to 4.3 cm and the relative decrease of water absorption time between control and sample of the water was up to 76%. Similarly, enzymes increasing the hydrophilicity of PA fibres such as from Nocardia sp., Beauveria sp. and F. solani hydrolysed the model substrate; however, there was no common enzyme activity (e.g. protease, esterase, amidase) which could be attributed to all these enzymes.
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PMID:New model substrates for enzymes hydrolysing polyethyleneterephthalate and polyamide fibres. 1662 19