Experimental and calculated shift in pK(a) upon binding of phosphotyrosine peptide to the SH2 domain of p56(lck).

Abstract:

:The pH dependence of the affinity of a 11-mer phosphotyrosine (pY) peptide (EPQpYEEIPIYL-NH2) for the SH2 domain of the tyrosine kinase p56(lck) was investigated with surface plasmon resonance (SPR). From SPR competition experiments the affinity in solution was obtained. The pH dependence of the affinity in solution can be well described by a proton linkage model with a single pK(a) shift upon binding, from 6.1 to 4.7. This shift is ascribed to the transition from the -2 to the -1 ionisation state of the tyrosine phosphate group. Based on the X-ray structure for the complex with Lck SH2, a pK(a) value of 5.3 for the bound pY peptide was computed, modelling the solvated protein as a system of point charges in a continuum. With the phosphate in the -2 state the binding energy is 1.8 kcal/mol more favourable than for the -1 state, corresponding to a 20-fold higher affinity. A proper charge is relevant in the design of potential therapeutic Lck SH2 ligands with mimics for the metabolically unstable tyrosine phosphate group.

journal_name

Bioorg Med Chem

authors

de Mol NJ,Gillies MB,Fischer MJ

doi

10.1016/s0968-0896(01)00407-2

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

1477-82

issue

5

eissn

0968-0896

issn

1464-3391

pii

S0968089601004072

journal_volume

10

pub_type

杂志文章
  • Design, synthesis, and structure-activity relationships of potent GPIIb/IIIa antagonists: discovery of FK419.

    abstract::The discovery of the non-peptide antiplatelet injectable agent FK419 is reported. Based on the beta-turn structure of RGD peptide sequences in the alpha chain of fibrinogen, which binds the glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of platelets to induce platelet aggregation, the prototype 2 was designed. Afte...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.03.056

    authors: Yamanaka T,Ohkubo M,Kuroda S,Nakamura H,Takahashi F,Aoki T,Mihara K,Seki J,Kato M

    更新日期:2005-07-01 00:00:00

  • Synthesis of indomethacin analogues for evaluation as modulators of MRP activity.

    abstract::Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00292-3

    authors: Maguire AR,Plunkett SJ,Papot S,Clynes M,O'Connor R,Touhey S

    更新日期:2001-03-01 00:00:00

  • Synthesis and structure-activity relationships of benzyloxyphenyl derivatives as a novel class of NCX inhibitors: effects on heart failure.

    abstract::In the context of heart failure and myocardial ischemia reperfusion, the activity of the sodium-calcium exchanger can lead to calcium overload, which in turn can lead to contractile dysfunction and arrhythmia. Therefore, NCX is an attractive target for treatment of heart failure and myocardial ischemia reperfusion. We...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.10.048

    authors: Kuramochi T,Kakefuda A,Yamada H,Ogiyama T,Taguchi T,Sakamoto S

    更新日期:2005-02-01 00:00:00

  • The comparison of characteristics between membrane-active antifungal peptide and its pseudopeptides.

    abstract::By the introduction of various amide surrogates, novel pseudopeptides corresponding to a membrane active depsipeptide were synthesized and their native characteristics compared with that of the peptide. The pseudopeptides had more resistance to serum proteases than the peptide and similar antimicrobial activities to t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(99)00176-5

    authors: Oh JE,Hong SY,Lee KH

    更新日期:1999-11-01 00:00:00

  • Synthesis and cancer cell cytotoxicity of substituted xanthenes.

    abstract::A series of substituted xanthenes was synthesized and screened for activity using DU-145, MCF-7, and HeLa cancer cell growth inhibition assays. The most potent compound, 9 g ([N,N-diethyl]-9-hydroxy-9-(3-methoxyphenyl)-9H-xanthene-3-carboxamide), was found to inhibit cancer cell growth with IC(50) values ranging from ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.01.018

    authors: Giri R,Goodell JR,Xing C,Benoit A,Kaur H,Hiasa H,Ferguson DM

    更新日期:2010-02-15 00:00:00

  • Molecular design of anti-MRSA agents based on the anacardic acid scaffold.

    abstract::A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.06.022

    authors: Green IR,Tocoli FE,Lee SH,Nihei K,Kubo I

    更新日期:2007-09-15 00:00:00

  • Comparing the efficacy of photodynamic and sonodynamic therapy in non-melanoma and melanoma skin cancer.

    abstract::Sonodynamic therapy (SDT) involves the activation of a non-toxic sensitiser drug using low-intensity ultrasound to produce cytotoxic reactive oxygen species (ROS). Given the low tissue attenuation of ultrasound, SDT provides a significant benefit over the more established photodynamic therapy (PDT) as it enables activ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.05.015

    authors: McEwan C,Nesbitt H,Nicholas D,Kavanagh ON,McKenna K,Loan P,Jack IG,McHale AP,Callan JF

    更新日期:2016-07-01 00:00:00

  • Protease inhibitors. Part 8: synthesis of potent Clostridium histolyticum collagenase inhibitors incorporating sulfonylated L-alanine hydroxamate moieties.

    abstract::A series of hydroxamates was prepared by reaction of alkyl/arylsulfonyl halides with N-2-chlorobenzyl-L-alanine, followed by conversion of the COOH moiety to the CONHOH group, with hydroxylamine in the presence of carbodiimides. Other structurally related compounds were obtained by reaction of N-2-chlorobenzyl-L-alani...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(99)00316-8

    authors: Scozzafava A,Supuran CT

    更新日期:2000-03-01 00:00:00

  • Synthesis and antimycobacterial properties of ring-substituted 6-hydroxynaphthalene-2-carboxanilides.

    abstract::In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Derivatives subs...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.03.018

    authors: Kos J,Nevin E,Soral M,Kushkevych I,Gonec T,Bobal P,Kollar P,Coffey A,O'Mahony J,Liptaj T,Kralova K,Jampilek J

    更新日期:2015-05-01 00:00:00

  • Acidic biphenyl derivatives: synthesis and biological activity of a new series of potent 5-HT(4) receptor antagonists.

    abstract::Serotonin (5-hydroxytryptamine, 5-HT) is an important signaling molecule in the central nervous system (CNS) and in non-neuronal tissues and organs. Serotonin mediates a positive chronotropic and inotropic response through 5-HT4 receptors in the atrium and ventricle of the heart. Recent investigations have revealed in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.09.004

    authors: Brudeli B,Andressen KW,Moltzau LR,Nilsen NO,Levy FO,Klaveness J

    更新日期:2013-11-15 00:00:00

  • Abenzyl 10-formyl-trideazafolic acid (abenzyl 10-formyl-TDAF): an effective inhibitor of glycinamide ribonucleotide transformylase.

    abstract::The synthesis of N-[7-(2-amino-3,4-dihydro-4-oxo-quinazolin-6-yl) -6-formyl-1-oxo-heptyl]-L-glutamic acid (2, abenzyl 10-formyl-5,8,10-trideazafolic acid) as a potential enzyme-assembled tight binding inhibitor of glycinamide ribonucleotide transformylase (GAR Tfase) or aminoimidazole carboxamide ribonucleotide transf...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(97)00123-5

    authors: Boger DL,Haynes NE,Warren MS,Ramcharan J,Marolewski AE,Kitos PA,Benkovic SJ

    更新日期:1997-09-01 00:00:00

  • Inhibition of monoamine oxidase B by selected benzimidazole and caffeine analogues.

    abstract::We have recently reported that a series of (E)-8-styrylcaffeines and (E)-2-styrylbenzimidazoles are moderate to very potent competitive inhibitors of monoamine oxidase B (MAO-B). The most potent member of the series was found to be (E)-8-(3-chlorostyryl)caffeine (CSC) with an enzyme-inhibitor dissociation constant (K(...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.03.046

    authors: van den Berg D,Zoellner KR,Ogunrombi MO,Malan SF,Terre'Blanche G,Castagnoli N Jr,Bergh JJ,Petzer JP

    更新日期:2007-06-01 00:00:00

  • Synthesis and anti-inflammatory activity of indole glucosinolates.

    abstract::The nitronate and nitrovinyl methods to synthesize indole glucosinolates (GLs) have been investigated. The results were applied to generally the most prevalent natural indole glucosinolates to synthesize 4-methoxyglucobrassicin (MGB) and neo-glucobrassicin (NGB) in moderate overall yield for the first time. The anti-i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.12.003

    authors: Vo QV,Trenerry C,Rochfort S,Wadeson J,Leyton C,Hughes AB

    更新日期:2014-01-15 00:00:00

  • A para-nitrophenol phosphonate probe labels distinct serine hydrolases of Arabidopsis.

    abstract::Activity-based protein profiling represents a powerful methodology to probe the activity state of enzymes under various physiological conditions. Here we present the development of a para-nitrophenol phosphonate activity-based probe with structural similarities to the potent agrochemical paraoxon. We demonstrate that ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.06.041

    authors: Nickel S,Kaschani F,Colby T,van der Hoorn RA,Kaiser M

    更新日期:2012-01-15 00:00:00

  • Preparation, antimicrobial evaluation, and mutagenicity of [2-hydroxyaryl]-[1-methyl-5-nitro-1H-2-imidazolyl]methanols , [5-tert-butyl-2-methylaminophenyl]-[1-methyl-5-nitro-1H-2-imidazo lyl]me thanol, and [2-hydroxyaryl]-[1-methyl-5-nitro-1H-2-imidazolyl

    abstract::Efficient preparations of the titled compounds are described, their antimicrobial activity and mutagenic properties being evaluated. Some of the studied compounds are nonmutagenic and present a MIC as low as some of the usual standards in the field. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(97)00138-7

    authors: Arredondo Y,Moreno-Mañas M,Pleixats R,Palacín C,Raga MM,Castelló JM,Ortiz JA

    更新日期:1997-10-01 00:00:00

  • meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

    abstract::Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.07.047

    authors: Reyes-Melo K,García A,Romo-Mancillas A,Garza-González E,Rivas-Galindo VM,Miranda LD,Vargas-Villarreal J,Favela-Hernández JMJ,Camacho-Corona MDR

    更新日期:2017-10-15 00:00:00

  • The new models of the human telomere d[AGGG(TTAGGG)3] in K+ solution.

    abstract::The human telomeric sequence d[AGGG(TTAGGG)(3)] has been found to form different types of G-quadruplex structures. NMR revealed that in Na(+) solution this 22 nucleotide (nt) sequence exhibits an antiparallel structure, whereas crystallographic studies in the presence of K(+) showed a dramatically different parallel s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.04.033

    authors: Xu Y,Noguchi Y,Sugiyama H

    更新日期:2006-08-15 00:00:00

  • Deoxyiminoalditols from aldonolactones--V. Preparation of the four stereoisomers of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three 1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.

    abstract::The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(96)00167-8

    authors: Godskesen M,Lundt I,Madsen R,Winchester B

    更新日期:1996-11-01 00:00:00

  • Chemical studies on antioxidant mechanism of tea catechins: analysis of radical reaction products of catechin and epicatechin with 2,2-diphenyl-1-picrylhydrazyl.

    abstract::Tea catechins, an important class of polyphenols, have been shown to have wide spectrum of antitumor activity believed to be due mainly to their antioxidative effect. In this study, the radical scavenging behavior of catechins on 2,2-diphenyl-1-picrylhydrazyl (DPPH) was studied. Two reaction products of (+)-catechin, ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00089-5

    authors: Sang S,Cheng X,Stark RE,Rosen RT,Yang CS,Ho CT

    更新日期:2002-07-01 00:00:00

  • Synthesis of egonol derivatives and their antimicrobial activities.

    abstract::Eighteen derivatives of egonol (A-R) were synthesized and evaluated for their antimicrobial activities against Staphylococcus aureus ATCC 29213, Bacillus subtilis ATCC 6633, Candida albicans ATCC 10231 and Escherichia coli ATCC 8739 microorganisms comparing with egonol. The obtained data reported that compound B exhib...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.12.044

    authors: Emirdağ-Öztürk S,Karayildirim T,Anil H

    更新日期:2011-02-01 00:00:00

  • Synthesis and biological activities of aminopyrimidyl-indoles structurally related to meridianins.

    abstract::The synthesis of new meridianin derivatives substituted at the C-5 position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. These compounds were tested for their kinase inhibitory potencies toward five kinases (CDK5/p25, CK1delta/epsilo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.05.017

    authors: Akue-Gedu R,Debiton E,Ferandin Y,Meijer L,Prudhomme M,Anizon F,Moreau P

    更新日期:2009-07-01 00:00:00

  • Synthesis and evaluation of novel amide amino-β-lactam derivatives as cholesterol absorption inhibitors.

    abstract::The β-lactam cholesterol absorption inhibitor ezetimibe is so far the only representative of this class of compounds on the market today. The goal of this work was to synthesize new amide ezetimibe analogs from trans-3-amino-(3R,4R)-β-lactam and to test their cytotoxicity and activity as cholesterol absorption inhibit...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.03.067

    authors: Dražić T,Sachdev V,Leopold C,Patankar JV,Malnar M,Hećimović S,Levak-Frank S,Habuš I,Kratky D

    更新日期:2015-05-15 00:00:00

  • Synthesis and hydrolytic behavior of two novel tripartate codrugs of naltrexone and 6beta-naltrexol with hydroxybupropion as potential alcohol abuse and smoking cessation agents.

    abstract::A codrug approach for simultaneous treatment of alcohol abuse and tobacco dependence is considered as very desirable because of substantial evidence that smoking is increased significantly during drinking, and that smoking is regarded as a behavioral 'cue' for the urge to consume alcohol. The purpose of this study was...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.06.018

    authors: Hamad MO,Kiptoo PK,Stinchcomb AL,Crooks PA

    更新日期:2006-10-15 00:00:00

  • Synthesis and biological activity of (24E)- and (24Z)-26-hydroxydesmosterol.

    abstract::Using 3β-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.07.015

    authors: Saini R,Kataeva O,Schmidt AW,Wang Y,Meljon A,Griffiths WJ,Knölker HJ

    更新日期:2013-09-15 00:00:00

  • New acridone-4-carboxylic acid derivatives as potential inhibitors of hepatitis C virus infection.

    abstract::A new class of compounds--acridone derivatives--was tested using the direct fluorometric helicase activity assay to determine the inhibitory properties of the derivatives towards the NS3 helicase of Hepatitis C virus (HCV). The compounds were also tested as putative transcription inhibitors of in vitro transcription b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.08.074

    authors: Stankiewicz-Drogon A,Palchykovska LG,Kostina VG,Alexeeva IV,Shved AD,Boguszewska-Chachulska AM

    更新日期:2008-10-01 00:00:00

  • Chalcone inhibitors of the NorA efflux pump in Staphylococcus aureus whole cells and enriched everted membrane vesicles.

    abstract::A library of 117 chalcones was screened for efflux pump inhibitory (EPI) activity against NorA mediated ethidium bromide efflux. Five of the chalcones (5-7, 9, and 10) were active and two chalcones (9 and 10) were equipotent to reserpine with IC(50)-values of 9.0 and 7.7 μM, respectively. Twenty chalcones were subsequ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.05.025

    authors: Holler JG,Slotved HC,Mølgaard P,Olsen CE,Christensen SB

    更新日期:2012-07-15 00:00:00

  • Chemical and enzymatic synthesis of fructose analogues as probes for import studies by the hexose transporter in parasites.

    abstract::Various D-fructose analogues modified at C-1 or C-6 positions were synthesized from D-glucose by taking advantage of the Amadori rearrangement or using the aldol condensation between dihydroxyacetone phosphate and appropriate aldehyde catalyzed by fructose 1,6-diphosphate aldolase from rabbit muscle. The affinities of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00018-3

    authors: Azéma L,Bringaud F,Blonski C,Périé J

    更新日期:2000-04-01 00:00:00

  • Phosphoenolpyruvate as a dual purpose reagent for integrated nucleotide/nicotinamide cofactor recycling.

    abstract::An efficient technique is presented which integrates cofactor dependent enzymic phosphorylation and dehydrogenation into a single, closed-loop system by employing phosphoenolpyruvate as the sacrificial reagent for sequential ATP and NAD+ recycling steps. Exemplary applications are developed for the synthesis of 6-phos...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(94)85012-7

    authors: Fessner WD,Sinerius G

    更新日期:1994-07-01 00:00:00

  • Combined NMR and molecular modeling study of an iduronic acid-containing trisaccharide related to antithrombotic heparin fragments.

    abstract::An iduronic acid-containing trisaccharide, methyl-O-(4-O-methyl-2,3,6-tri-O-sulfo-alpha-D-glucopyranosyl-(1-->4)-O- (2-O-sulfo-alpha-L-idopyranosyluronic acid)-(1-->4)-O-2,6-di-O-sulfo-alpha-D-glucopyranoside, related to antithrombotic heparin fragments has been subjected to a combined NMR and molecular modeling inves...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(97)00087-4

    authors: Cros S,Petitou M,Sizun P,Pérez S,Imberty A

    更新日期:1997-07-01 00:00:00

  • Synthesis and antioxidant activity evaluation of new 7-aryl or 7-heteroarylamino-2,3-dimethylbenzo[b]thiophenes obtained by Buchwald-Hartwig C-N cross-coupling.

    abstract::New 7-aryl or 7-heteroarylamino-2,3-dimethylbenzo[b]thiophenes were prepared by palladium-catalyzed Buchwald-Hartwig cross-coupling of 7-bromo or 7-amino-2,3-dimethylbenzo[b]thiophenes, previously prepared by us, with substituted (4-methoxy or 3,4-dimethoxy) anilines and 3-aminopyridine or with substituted (3-methoxy ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.11.035

    authors: Queiroz MJ,Ferreira IC,Calhelha RC,Estevinho LM

    更新日期:2007-02-15 00:00:00