Cloning, isolation and characterization of the Thermotoga maritima KDPG aldolase.

Abstract:

:The Thermotoga maritima aldolase gene has been cloned into a T7 expression vector and overexpressed in Escherichia coli. The preparation yields 470 UL(-1) of enzyme at a specific activity of 9.4 U mg(-1). During retroaldol cleavage of KDPG, the enzyme shows a k(cat) that decreases with decreasing temperature. A more than offsetting decrease in K(m) yields an enzyme that is more efficient at 40 degrees C than at 70 degrees C. The substrate specificity of the enzyme was evaluated in the synthetic direction with a range of aldehyde substrates. Although the protein shows considerable structural homology to KDPG aldolases from mesophilic sources, significant differences in substrate specificity exist. A preparative scale reaction between 2-pyridine carboxaldehyde and pyruvate provided product of the same absolute configuration as mesophilic enzymes, but with diminished stereoselectivity.

journal_name

Bioorg Med Chem

authors

Griffiths JS,Wymer NJ,Njolito E,Niranjanakumari S,Fierke CA,Toone EJ

doi

10.1016/s0968-0896(01)00307-8

subject

Has Abstract

pub_date

2002-03-01 00:00:00

pages

545-50

issue

3

eissn

0968-0896

issn

1464-3391

pii

S0968089601003078

journal_volume

10

pub_type

杂志文章
  • Antifungal polyketide derivatives from the endophytic fungus Aplosporella javeedii.

    abstract::Six new polyketides aplojaveediins A-F (1-6) were isolated from the endophytic fungus Aplosporella javeedii associated with the host plant Orychophragmus violaceus (Brassicaceae). The structures of the new metabolites were elucidated by analysis of their NMR and MS data. Compound 1 exhibited antifungal activity agains...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115456

    authors: Gao Y,Wang L,Kalscheuer R,Liu Z,Proksch P

    更新日期:2020-05-15 00:00:00

  • Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors.

    abstract::A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with I...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.01.031

    authors: Makhaeva GF,Boltneva NP,Lushchekina SV,Serebryakova OG,Stupina TS,Terentiev AA,Serkov IV,Proshin AN,Bachurin SO,Richardson RJ

    更新日期:2016-03-01 00:00:00

  • Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors.

    abstract::A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.08.047

    authors: Angapelly S,Ramya PVS,Angeli A,Del Prete S,Capasso C,Arifuddin M,Supuran CT

    更新日期:2017-10-15 00:00:00

  • Synthesis and biological evaluation of indazolo[4,3-bc][1,5]naphthyridines (10-aza-pyrazolo[3,4,5-kl]acridines): a new class of antitumor agents.

    abstract::A series of potential DNA-binding antitumor agents, 2-[omega-(alkylamino)alkyl]-9-methoxy-5-nitro-2,6-dihydroindazolo[4,3-bc][1,5]naphthyridines (2a-f), 10-aza derivatives of PZA, has been prepared by condensation of 9-chloro-2-methoxy-6-nitro-5,10-dihydrobenzo[b][1,5]naphthyridin-10-one (6) with the appropriate (omeg...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.08.020

    authors: Magnano A,Sparapani S,Lucciarini R,Michela M,Amantini C,Santoni G,Antonini I

    更新日期:2004-11-15 00:00:00

  • Synthesis, biological evaluation and molecular docking studies of benzyloxyacetohydroxamic acids as LpxC inhibitors.

    abstract::The inhibition of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represents a promising strategy to combat infections caused by multidrug-resistant Gram-negative bacteria. In order to elucidate the functional groups being important for the inhibition of LpxC, the structure of our previousl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.12.057

    authors: Szermerski M,Melesina J,Wichapong K,Löppenberg M,Jose J,Sippl W,Holl R

    更新日期:2014-02-01 00:00:00

  • Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors.

    abstract::A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the minor groove of nucleic acids was synthesized. These oligopeptides contained different numbers of thiazole units presenting dimethylaminopropyl or EDTA moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus. The inhi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00029-8

    authors: Ryabinin VA,Zakharova OD,Yurchenko EY,Timofeeva OA,Martyanov IV,Tokarev AA,Belanov EF,Bormotov NI,Tarrago-Litvak L,Andreola ML,Litvak S,Nevinsky GA,Sinyakov AN

    更新日期:2000-05-01 00:00:00

  • Emerging targets and new small molecule therapies in Parkinson's disease treatment.

    abstract::Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Due to a rapidly aging society worldwide, PD morbidity is on the rise; however, the treatment of PD with conventional drugs carries serious adverse reactions and cannot fix the root cause of PD, the degeneration of dopamin...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmc.2016.02.030

    authors: Zhang H,Tong R,Bai L,Shi J,Ouyang L

    更新日期:2016-04-01 00:00:00

  • Search for alpha-helical propensity in the receptor-bound conformation of glucagon-like peptide-1.

    abstract::To elucidate the receptor-bound conformation of glucagon-like peptide-1 (GLP-1), a series of conformationally constrained GLP-1 analogues were synthesized by introducing lactam bridges between Lys(i) and Glu(i)(+4) to form alpha-helices at various positions. The activity and affinity of these analogues to GLP-1 recept...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.10.006

    authors: Murage EN,Schroeder JC,Beinborn M,Ahn JM

    更新日期:2008-12-01 00:00:00

  • N2-Trimethylacetyl substituted and unsubstituted-N4-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: design, cellular receptor tyrosine kinase inhibitory activities and in vivo evaluation as antiangiogenic, antimetastati

    abstract::Six novel N(4)-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines and their N(2)-trimethylacetyl substituted analogs were synthesized as receptor tyrosine kinase (RTK) inhibitors. A microwave-mediated Sonogashira reaction was used as a key step for the synthesis of these compounds. Biol...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.12.045

    authors: Gangjee A,Namjoshi OA,Yu J,Ihnat MA,Thorpe JE,Bailey-Downs LC

    更新日期:2013-03-01 00:00:00

  • Biodistribution of (125)I-labeled polymeric vaccine carriers after subcutaneous injection.

    abstract::Polymeric nanoparticles (NPs) comprised of hydrophilic poly(γ-glutamic acid) in the main chain and hydrophobic phenylalanine in the side chain (γ-PGA-Phe) are a promising vaccine carrier for various kinds of diseases. However, little is known about the fate of subcutaneously administered γ-PGA-Phe NPs. Therefore, we n...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.06.021

    authors: Toita R,Kanai Y,Watabe H,Nakao K,Yamamoto S,Hatazawa J,Akashi M

    更新日期:2013-09-01 00:00:00

  • Design, synthesis and biological evaluation of isochroman-4-one hybrids bearing piperazine moiety as antihypertensive agent candidates.

    abstract::7,8-Dihydroxy-3-methyl-isochromanone-4 (XJP), is a polyphenolic natural product with moderate antihypertensive activity. To obtain new agents with stronger potency and safer profile, we employed XJP and naftopidil as the lead compounds to design and synthesize a novel class of hybrids as antihypertensive agent candida...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.05.004

    authors: Xie S,Li X,Yu H,Zhang P,Wang J,Wang C,Xu S,Wu Z,Liu J,Zhu Z,Xu J

    更新日期:2019-07-01 00:00:00

  • Synthesis and activity of nucleoside-based antiprotozoan compounds.

    abstract::Parasitic protozoa employ a salvage pathway to synthesize purines and generate essential active nucleotides, whereas mammals are capable of their de novo biosynthesis. This difference provides opportunity for the design of potential new antiprotozoan compounds. A series of 47 adenosine analogues was prepared with modi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.02.016

    authors: Tran HA,Zheng Z,Wen X,Manivannan S,Pastor A,Kaiser M,Brun R,Snyder FF,Back TG

    更新日期:2017-04-01 00:00:00

  • DNA double helix destabilizing properties of cyclobisintercaland compounds and competition with a single strand binding protein.

    abstract::The DNA helix destabilizing activity of a series of cyclobisintercaland compounds (CBIs) has been evaluated by measuring their ability to displace a 32P-labelled oligonucleotide primer (17-mer) hybridized to the single stranded DNA of M13. This destabilizing activity appears to be strongly dependent on the cyclic stru...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(99)00283-7

    authors: Teulade-Fichou MP,Fauquet M,Baudoin O,Vigneron JP,Lehn JM

    更新日期:2000-01-01 00:00:00

  • Generation of hazardous methyl azide and its application to synthesis of a key-intermediate of picarbutrazox, a new potent pesticide in flow.

    abstract::Generation and reactions of methyl azide (MeN3) were successfully performed by using a flow reactor system, demonstrating that the flow method serves as a safe method for handling hazardous explosive methyl azide. The reaction of NaN3 and Me2SO4 in a flow reactor gave a MeN3 solution, which was used for Huisgen reacti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.07.005

    authors: Ichinari D,Nagaki A,Yoshida JI

    更新日期:2017-12-01 00:00:00

  • Selective activity against Mycobacteriumtuberculosis of new quinoxaline 1,4-di-N-oxides.

    abstract::New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 microg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.10.086

    authors: Vicente E,Pérez-Silanes S,Lima LM,Ancizu S,Burguete A,Solano B,Villar R,Aldana I,Monge A

    更新日期:2009-01-01 00:00:00

  • QSAR of the testosterone binding globulin affinity by means of correlation weighting of local invariants of the graph of atomic orbitals.

    abstract::Numerical values of the testosterone binding globulin affinity have been modeled as a mathematical function of molecular structure in two versions of molecular structure elucidation: first, by hydrogen-filled molecular graphs (HFG); second, by the so-called graphs of atomic orbitals (GAO). Increased orders of Morgan e...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.07.059

    authors: Raska I Jr,Toropov A

    更新日期:2005-12-15 00:00:00

  • Benzene-1,3-dicarboxylic acid 2,5-dimethylpyrrole derivatives as multiple inhibitors of bacterial Mur ligases (MurC-MurF).

    abstract::Enzymes catalyzing the biosynthesis of bacterial peptidoglycan represent traditionally a collection of highly selective targets for novel antibacterial drug design. Four members of the bacterial Mur ligase family-MurC, MurD, MurE and MurF-are involved in the intracellular steps of peptidoglycan biosynthesis, catalyzin...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.05.058

    authors: Perdih A,Hrast M,Barreteau H,Gobec S,Wolber G,Solmajer T

    更新日期:2014-08-01 00:00:00

  • Acetyltransfer in natural product biosynthesis--functional cloning and molecular analysis of vinorine synthase.

    abstract::Vinorine synthase (EC 2.3.1.160) catalyses the acetyl-CoA- or CoA-dependent reversible formation of the alkaloids vinorine (or 11-methoxy-vinorine) and 16-epi-vellosimine (or gardneral). The forward reaction leads to vinorine, which is a direct biosynthetic precursor along the complex pathway to the monoterpenoid indo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.02.029

    authors: Bayer A,Ma X,Stöckigt J

    更新日期:2004-05-15 00:00:00

  • Biocatalytic combinatorial synthesis.

    abstract::Combinatorial biocatalysis, based on a principle of the combinatorial use of biosynthetic steps rather than the combinatorial use of reagents, offers a complementary approach to combinatorial chemistry, which, used individually or in connection with synthetic organic transformations, provides access to analogues not r...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(99)00145-5

    authors: Krstenansky JL,Khmelnitsky Y

    更新日期:1999-10-01 00:00:00

  • Design, synthesis and herbicidal activity of new iron chelating motifs for HPPD-inhibitors.

    abstract::HPPD (p-hydroxyphenylpyruvate dioxygenase) is a herbicidal target that all major companies active in plant protection research have worked on intensely in the last decade. Several modern herbicides with this mode of action have been introduced recently, or are currently in development. The activity of all commercializ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.11.006

    authors: Witschel M

    更新日期:2009-06-15 00:00:00

  • An approach to identifying novel substrates of bacterial arylamine N-acetyltransferases.

    abstract::Arylamine N-acetyltransferases (NATs) catalyse the acetylation of arylamine, arylhydrazine and arylhydroxylamine substrates by acetyl Coenzyme A. NAT has been discovered in a wide range of eukaryotic and prokaryotic species. Although prokaryotic NATs have been implicated in xenobiotic metabolism, to date no endogenous...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00642-9

    authors: Brooke EW,Davies SG,Mulvaney AW,Pompeo F,Sim E,Vickers RJ

    更新日期:2003-04-03 00:00:00

  • Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands.

    abstract::Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K(i)=5.5+/-1.1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.06.070

    authors: Baumann CA,Mu L,Wertli N,Krämer SD,Honer M,Schubiger PA,Ametamey SM

    更新日期:2010-08-15 00:00:00

  • Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones.

    abstract::A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycem...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(03)00142-1

    authors: Ram VJ,Farhanullah,Tripathi BK,Srivastava AK

    更新日期:2003-05-29 00:00:00

  • Design, synthesis, and biological evaluation of novel 4-oxobenzo[d]1,2,3-triazin-benzylpyridinum derivatives as potent anti-Alzheimer agents.

    abstract::Novel 4-oxobenzo[d]1,2,3-triazin derivatives bearing pyridinium moiety 6a-q were synthesized and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Most of the synthesized compounds showed good inhibitory activity against AChE. Among the synthesized compounds, the compound 6j exhibited the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.05.023

    authors: Hosseini F,Ramazani A,Mohammadi-Khanaposhtani M,Barazandeh Tehrani M,Nadri H,Larijani B,Mahdavi M

    更新日期:2019-07-01 00:00:00

  • Structural insights into the hot spot amino acid residues of mushroom tyrosinase for the bindings of thujaplicins.

    abstract::Tyrosinase inhibitors are important agents for cosmetic products. We examined here the inhibitory effects of three isomers of thujaplicins (α, β and γ) on mushroom tyrosinase and analyzed their binding modes using a homology model from the crystal structure of Streptomyces castaneoglobisporus tyrosinase (PDB ID: 1wx2)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.08.056

    authors: Takahashi S,Kamiya T,Saeki K,Nezu T,Takeuchi S,Takasawa R,Sunaga S,Yoshimori A,Ebizuka S,Abe T,Tanuma S

    更新日期:2010-11-15 00:00:00

  • Chemical synthesis, cytotoxicity, selectivity and bioavailability of 5α-androstane-3α,17β-diol derivatives.

    abstract::Aminosteroid derivatives represent a new family of compounds with promising antiproliferative activity over different cancer cell lines. Among all the aminosteroid derivatives synthesised in our laboratory, we have identified E-37P as one of the more potent when tested in vitro. Unfortunately, the pharmacokinetic prop...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.09.026

    authors: Ayan D,Maltais R,Hospital A,Poirier D

    更新日期:2014-11-01 00:00:00

  • Comparative reactivity analysis of small-molecule thiol surrogates.

    abstract::Targeted covalent inhibitors represent an increasingly popular approach to modulate challenging drug targets. Since covalent and non-covalent interactions are both contributing to the affinity of these compounds, evaluation of their reactivity is a key-step to find feasible warheads. There are well-established HPLC- a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115357

    authors: Petri L,Ábrányi-Balogh P,Varga PR,Imre T,Keserű GM

    更新日期:2020-04-01 00:00:00

  • A quencher-free molecular beacon design based on pyrene excimer fluorescence using pyrene-labeled UNA (unlocked nucleic acid).

    abstract::A quencher-free molecular beacon capable of generating pyrene excimer fluorescence has been constructed using strategically positioned pyrene-UNA monomers. Hybridization of a fully complementary RNA target was accompanied by a pyrene excimer emission increase of more than 900%, and detection of RNA in living cells was...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.04.062

    authors: Karlsen KK,Okholm A,Kjems J,Wengel J

    更新日期:2013-10-15 00:00:00

  • Covalent inhibition of SUMO and ubiquitin-specific cysteine proteases by an in situ thiol-alkyne addition.

    abstract::Posttranslational modification of proteins with ubiquitin and ubiquitin-like modifiers such as SUMO can be reverted by specific proteases, also referred to as deubiquitinases and isopeptidases, most of which are cysteine-dependent. We have found that the replacement of the conserved C-terminal glycine with propargylam...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.02.039

    authors: Sommer S,Weikart ND,Linne U,Mootz HD

    更新日期:2013-05-01 00:00:00

  • Synthesis and evaluation of macrocyclic amino acid derivatives for tumor imaging by gallium-68 positron emission tomography.

    abstract::(68)Ga PET imaging in clinical oncology represents a notable development because the availability of (68)Ga is not dependent on a cyclotron. Furthermore, labeled amino acid derivatives have been proven to be useful for the imaging many tumor types. In the present study, we synthesized β-aminoalanine, γ-aminohomoalanin...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.09.022

    authors: Shetty D,Jeong JM,Ju CH,Kim YJ,Lee JY,Lee YS,Lee DS,Chung JK,Lee MC

    更新日期:2010-11-01 00:00:00