当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Insights into the substrate specificity of the MutT pyrophosphohydrolase using structural analogues of 8-oxo-2'-deoxyguanosine nucleotide.

Insights into the substrate specificity of the MutT pyrophosphohydrolase using structural analogues of 8-oxo-2'-deoxyguanosine nucleotide.

Abstract：

:The bacterial repair enzyme MutT hydrolyzes the damaged nucleotide OdGTP (the 5'-triphosphate derivative of 8-oxo-2'-deoxyguanosine; OdG), which is a known mutagen and has been linked to antibacterial action. Previous work has indicated important roles for the C8-oxygen, N7-hydrogen, and C2-exocyclic amine during OdGTP recognition by MutT. In order to gain a more nuanced understanding of the contribution of these three sites to the overall activity of MutT, we determined the reaction parameters for dGTP, OdGTP, and nine of their analogues using steady state kinetics. Our results indicate that overall high reaction efficiencies can be achieved despite altering any one of these sites. However, altering two or more sites leads to a significant decrease in efficiency. The data also suggest that, similar to another bacterial OdG repair enzyme, MutM, a specific carbonyl in the enzyme can not only promote activity by forming an active site hydrogen bond with the N7-hydrogen of OdGTP, but can also hinder activity through electrostatic repulsion with the N7-lone pair of dGTP.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Hamm ML,McFadden EJ,Ghio M,Lindell MA,Gerien KS,O'Handley SF

doi

10.1016/j.bmcl.2016.02.083

subject

Has Abstract

pub_date

2016-04-15 00:00:00

pages

2014-7

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30208-6

journal_volume

26

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Studies on the interactions between some flavonols and cyclodextrins.

    abstract：:The interactions of some natural flavonols with alpha, beta- and gamma-Cds have been investigated. Guest molecules were galangin, kaempferol and quercetin. Inclusion complexes were prepared by kneading and freeze-drying. The complexes were characterized using different physico-chemical methods based on differential sc...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.08.067

    authors： Bergonzi MC,Bilia AR,Di Bari L,Mazzi G,Vincieri FF

    更新日期：2007-11-01 00:00:00

  • The preparation of 2,6-disubstituted pyridinyl phosphine oxides as novel anti-cancer agents.

    abstract：:A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is imp...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.02.091

    authors： Lam KH,Gambari R,Yuen MC,Kan CW,Chan P,Xu L,Tang W,Chui CH,Cheng GY,Wong RS,Lau FY,Tong CS,Chan AK,Lai PB,Kok SH,Cheng CH,Chan AS,Tang JC

    更新日期：2009-04-15 00:00:00

  • A chromism-based assay (CHROBA) technique for in situ detection of protein kinase activity.

    abstract：:A unique chromism-based assay technique (CHROBA) using photochromic spiropyran-containing peptides has been firstly established for detection of protein kinase A-catalyzed phosphorylation. The alternative method has advantages that avoid isolation and/or immobilization of kinase substrates to remove excess reagents in...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.01.035

    authors： Tomizaki KY,Jie X,Mihara H

    更新日期：2005-03-15 00:00:00

  • Cytotoxic and PTP1B inhibitory activities from Erythrina abyssinica.

    abstract：:Bioassay-guided fractionation of the EtOAc extract of the stem bark of Erythrina abyssinica (Leguminosae) resulted in the isolation of three new (1-3), along with 12 known (4-15) pterocarpan derivatives. Their chemical structures were determined by physicochemical and spectroscopic data analysis (IR, UV, [alpha](D), C...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.108

    authors： Nguyen PH,Le TV,Thuong PT,Dao TT,Ndinteh DT,Mbafor JT,Kang KW,Oh WK

    更新日期：2009-12-01 00:00:00

  • Synthesis of a cosalane analog with an extended polyanionic pharmacophore conferring enhanced potency as an anti-HIV agent.

    abstract：:A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 microM as an inhibi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00121-8

    authors： Cushman M,Insaf S,Ruell JA,Schaeffer CA,Rice WG

    更新日期：1998-04-07 00:00:00

  • Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways.

    abstract：:A thiazolidine-2,4-dione derivative, 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione (2), was identified as a dual inhibitor of the Raf/MEK/ extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades. The discovered compound inhibited cell prolifera...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.030

    authors： Li Q,Wu J,Zheng H,Liu K,Guo TL,Liu Y,Eblen ST,Grant S,Zhang S

    更新日期：2010-08-01 00:00:00

  • Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives.

    abstract：:A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.11.049

    authors： Yoakim C,Bonneau PR,Déziel R,Doyon L,Duan J,Guse I,Landry S,Malenfant E,Naud J,Ogilvie WW,O'Meara JA,Plante R,Simoneau B,Thavonekham B,Bös M,Cordingley MG

    更新日期：2004-02-09 00:00:00

  • A highly atom economic, chemo-, regio- and stereoselective synthesis and evaluation of spiro-pyrrolothiazoles as antitubercular agents.

    abstract：:The 1,3-dipolar cycloaddition of azomethine ylides derived from substituted isatins and 1,3-thiazolane-4-carboxylic acid to a series of 1-methyl-3,5-bis[(E)-arylmethylidene]-tetrahydro-4(1H)-pyridinones afforded novel spiro-pyrrolothiazoles chemo-, regio- and stereoselectively in quantitative yields. These compounds w...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.10.107

    authors： Karthikeyan SV,Bala BD,Raja VP,Perumal S,Yogeeswari P,Sriram D

    更新日期：2010-01-01 00:00:00

  • Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists.

    abstract：:A series of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles was designed and synthesized as anticonvulsant agents. Conformational analysis and superimposition of energy minima conformers of the designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main proposed benzodia...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.04.018

    authors： Zarghi A,Faizi M,Shafaghi B,Ahadian A,Khojastehpoor HR,Zanganeh V,Tabatabai SA,Shafiee A

    更新日期：2005-06-15 00:00:00

  • Discovery of a potent and selective series of pyrazole bacterial methionyl-tRNA synthetase inhibitors.

    abstract：:Starting with a micromolar lead identified from high-throughput screening, a series of pyrazoles were discovered with significantly improved potency on bacterial methionyl-tRNA synthetase and selectivity over human methionyl-tRNA synthetase. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00298-1

    authors： Finn J,Mattia K,Morytko M,Ram S,Yang Y,Wu X,Mak E,Gallant P,Keith D

    更新日期：2003-07-07 00:00:00

  • Carbonic anhydrase inhibitors: X-ray crystallographic studies for the binding of 5-amino-1,3,4-thiadiazole-2-sulfonamide and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide to human isoform II.

    abstract：:The X-ray crystal structures of 5-amino-1,3,4-thiadiazole-2-sulfonamide (the acetazolamide precursor) and 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide in complex with the human isozyme II of carbonic anhydrase (CA, EC 4.2.1.1) are reported. The thiadiazole-sulfonamide moiety of the tw...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.09.022

    authors： Menchise V,De Simone G,Di Fiore A,Scozzafava A,Supuran CT

    更新日期：2006-12-15 00:00:00

  • New highly selective inhibitors of class II fructose-1,6-bisphosphate aldolases.

    abstract：:Phosphoglycolo amidoxime and phosphoglycolo hydrazide, two new derivatives of phosphoglycolic acid, were synthesised and successfully tested as selective competitive inhibitors of class II FBP-aldolases. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.03.040

    authors： Fonvielle M,Weber P,Dabkowska K,Therisod M

    更新日期：2004-06-07 00:00:00

  • Photo-controlled release of fipronil from a coumarin triggered precursor.

    abstract：:Developing efficient controlled release system of insecticide can facilitate the better use of insecticide. We described here a first example of photo-controlled release of an insecticide by linking fipronil with photoresponsive coumarin covalently. The generated coumarin-fipronil (CF) precursor could undergo cleavage...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.03.091

    authors： Gao Z,Yuan P,Wang D,Xu Z,Li Z,Shao X

    更新日期：2017-06-01 00:00:00

  • Design, synthesis, and biological activity of novel purine and bicyclic pyrimidine factor Xa inhibitors.

    abstract：:The synthesis of amidinoaryloxy 9-benzyl-8-methyl-9H-purine, 7,8-dihydropteridine-6(5H)-one and 5,7-dihydropyrimido[4,5-b][1,4]oxazine-6-one inhibitors of Factor Xa is described. These compounds show nanomolar potency against FXa and maintain high selectivity over thrombin and trypsin. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00386-2

    authors： Buckman BO,Mohan R,Koovakkat S,Liang A,Trinh L,Morrissey MM

    更新日期：1998-08-18 00:00:00

  • C1 and N5 derivatives of cerpegin: synthesis of a new series based on structure-activity relationships to optimize their inhibitory effect on 20S proteasome.

    abstract：:Thirty-two new derivatives of cerpegin (1,1,5-trimethylfuro[3,4-c]pyridine-3,4-dione) were designed and synthesized in high yield by a new method, combining several C(1) and N(5) substituents. All compounds were tested for their inhibitory effect on the CT-L, T-L and PA proteolytic activities of a purified mammalian 2...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.079

    authors： Hovhannisyan A,Pham TH,Bouvier D,Qin L,Melikyan G,Reboud-Ravaux M,Bouvier-Durand M

    更新日期：2013-05-01 00:00:00

  • Kinetic investigation of human 5-lipoxygenase with arachidonic acid.

    abstract：:Human 5-lipoxygenase (5-LOX) is responsible for the formation of leukotriene (LT)A4, a pivotal intermediate in the biosynthesis of the leukotrienes, a family of proinflammatory lipid mediators. 5-LOX has thus gained attention as a potential drug target. However, details of the kinetic mechanism of 5-LOX are still obsc...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.06.025

    authors： Mittal M,Kumar RB,Balagunaseelan N,Hamberg M,Jegerschöld C,Rådmark O,Haeggström JZ,Rinaldo-Matthis A

    更新日期：2016-08-01 00:00:00

  • Identification of aryl dihydrouracil derivatives as palm initiation site inhibitors of HCV NS5B polymerase.

    abstract：:Aryl dihydrouracil derivatives were identified from high throughput screening as potent inhibitors of HCV NS5B polymerase. The aryl dihydrouracil derivatives were shown to be non-competitive with respect to template RNA and elongation nucleotide substrates. They demonstrated genotype 1 specific activity towards HCV NS...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.017

    authors： Liu Y,Lim BH,Jiang WW,Flentge CA,Hutchinson DK,Madigan DL,Randolph JT,Wagner R,Maring CJ,Kati WM,Molla A

    更新日期：2012-06-01 00:00:00

  • Synthesis and antifungal activities of new fluconazole analogues with azaheterocycle moiety.

    abstract：:A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.04.038

    authors： Lebouvier N,Pagniez F,Duflos M,Le Pape P,Na YM,Le Baut G,Le Borgne M

    更新日期：2007-07-01 00:00:00

  • Fluorometric detection of adenine in target DNA by exciplex formation with fluorescent 8-arylethynylated deoxyguanosine.

    abstract：:We demonstrated an intriguing method to discriminate adenine by incident appearance of an intense new emission via exciplex formation in hybridization of target DNA with newly designed fluorescent 8-arylethynylated deoxyguanosine derivatives. We described the synthesis of such highly electron donating fluorescent guan...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.011

    authors： Saito Y,Kugenuma K,Tanaka M,Suzuki A,Saito I

    更新日期：2012-06-01 00:00:00

  • Synthesis, antimycobacterial and antibacterial activity of ciprofloxacin derivatives containing a N-substituted benzyl moiety.

    abstract：:We report herein the design and synthesis of a series of novel ciprofloxacin (CPFX) derivatives with remarkable improvement in lipophilicity by introducing a substituted benzyl moiety to the N atom on the C-7 piperazine ring of CPFX. Antimycobacterial and antibacterial activity of the newly synthesized compounds was e...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.07.040

    authors： Wang S,Jia XD,Liu ML,Lu Y,Guo HY

    更新日期：2012-09-15 00:00:00

  • Discovery of a novel melanin concentrating hormone receptor 1 (MCHR1) antagonist with reduced hERG inhibition.

    abstract：:An initial SAR study resulted in the identification of the novel, potent MCHR1 antagonist 2. After further profiling, compound 2 was discovered to be a potent inhibitor of the hERG potassium channel, which prevented its further development. Additional optimization of this structure resulted in the discovery of the pot...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.04.006

    authors： Mihalic JT,Fan P,Chen X,Chen X,Fu Y,Motani A,Liang L,Lindstrom M,Tang L,Chen JL,Jaen J,Dai K,Li L

    更新日期：2012-06-01 00:00:00

  • Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.

    abstract：:Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.12.028

    authors： Ghosh AK,Kumaragurubaran N,Hong L,Kulkarni S,Xu X,Miller HB,Reddy DS,Weerasena V,Turner R,Chang W,Koelsch G,Tang J

    更新日期：2008-02-01 00:00:00

  • 2-Cyano-4-fluoro-1-thiovalylpyrrolidine analogues as potent inhibitors of DPP-IV.

    abstract：:We report the synthesis and biological activity of a series of 2-cyano-4-fluoro-1-thiovalylpyrrolidine inhibitors of DPP-IV. Within this series, compound 19 provided a potent, selective, and orally active DPP-IV inhibitor which demonstrated a very long duration of action in both rat and dog. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.08.050

    authors： Haffner CD,McDougald DL,Reister SM,Thompson BD,Conlee C,Fang J,Bass J,Lenhard JM,Croom D,Secosky-Chang MB,Tomaszek T,McConn D,Wells-Knecht K,Johnson PR

    更新日期：2005-12-01 00:00:00

  • Polarization in the structures of uracil and thiouracils: Implication for binding with orotidine 5'-monophosphate decarboxylase.

    abstract：:The structures of the uracil and thiouracils were examined using NMR spectroscopy and crystal structure data when available. The relationships between the extent of polarization and the C5-C6 bond length as well as the H5-H6 coupling constants were probed. It was found that the bond length and coupling constants corre...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.08.109

    authors： Huang S,Gronert S,Wu W

    更新日期：2011-11-01 00:00:00

  • Cyclohexanedione herbicides are inhibitors of rat heart acetyl-CoA carboxylase.

    abstract：:Acetyl CoA carboxylase (ACC) catalyzes the carboxylation of acetyl CoA to form malonyl CoA. In skeletal muscle and heart, malonyl CoA functions to regulate lipid oxidation by inhibition of carnitine palmitoyltransferase-1, an enzyme which controls the entry of long chain fatty acids into mitochondria. We have found th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00664-4

    authors： Seng TW,Skillman TR,Yang N,Hammond C

    更新日期：2003-10-06 00:00:00

  • Identification of novel estrogen receptor (ER) agonists that have additional and complementary anti-cancer activities via ER-independent mechanism.

    abstract：:In this study, a series of bis(4-hydroxy)benzophenone oxime ether derivatives such as 12c, 12e and 12h were identified as novel estrogen receptor (ER) agonists that have additional and complementary anti-proliferative activities via ER-independent mechanism in cancer cells. These compounds are expected to overcome the...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.01.089

    authors： Kim T,Kim HI,An JY,Lee J,Lee NR,Heo J,Kim JE,Yu J,Lee YS,Inn KS,Kim NJ

    更新日期：2016-04-01 00:00:00

  • Total synthesis and cytotoxic activities of longamide B, longamide B methyl ester, hanishin, and their analogues.

    abstract：:The marine alkaloids, longamide B (1), longamide B methyl ester (2), hanishin (3), and a series of non-naturally occurring analogues were synthesized in an efficient manner from inexpensive commercially available dl-aspartic acid dimethyl ester. The cytotoxicities of these natural products (1-3) and their analogues (9...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.11.069

    authors： Zhao DG,Ma YY,Peng W,Zhou AY,Zhang Y,Ding L,Du Z,Zhang K

    更新日期：2016-01-01 00:00:00

  • Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit.

    abstract：:A series of new imines and amines have been synthesized by condensation of 1H-3-ferrocenyl-1-phenylpyrazole-4-carboxaldehyde with the corresponding amines, followed by reduction with sodium borohydride. The synthesized compounds have been screened for their in vitro antimicrobial activity against 11 bacteria and three...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.01.006

    authors： Damljanović I,Vukićević M,Radulović N,Palić R,Ellmerer E,Ratković Z,Joksović MD,Vukićević RD

    更新日期：2009-02-15 00:00:00

  • Design and efficient synthesis of A-278637 derivatives as potential potassium channel opener.

    abstract：:A series of thieno[3,2-b]quinoline derivatives designed based on A-278637 scaffold, were synthesized efficiently via one-pot three-component reaction under solvent-free and catalyst-free conditions. This work provides a new compound library with potential biological activity for biomedical screening. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.10.127

    authors： Li T,Feng X,Yao C,Yu C,Jiang B,Tu S

    更新日期：2011-01-01 00:00:00

  • Discovery of cariprazine (RGH-188): a novel antipsychotic acting on dopamine D3/D2 receptors.

    abstract：:Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) receptors. Several members of this group showed excellent pharmacokinetic and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.03.104

    authors： Agai-Csongor E,Domány G,Nógrádi K,Galambos J,Vágó I,Keserű GM,Greiner I,Laszlovszky I,Gere A,Schmidt E,Kiss B,Vastag M,Tihanyi K,Sághy K,Laszy J,Gyertyán I,Zájer-Balázs M,Gémesi L,Kapás M,Szombathelyi Z

    更新日期：2012-05-15 00:00:00