当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Expanding the recognition of the minor groove of DNA by incorporation of beta-alanine in hairpin polyamides.

Expanding the recognition of the minor groove of DNA by incorporation of beta-alanine in hairpin polyamides.

Abstract：

:In order to expand the recognition code by hairpin polyamides to include DNA sequences of the type 5'-CWWC-3' two polyamides, PyPyPyPy-(R)(H2N)gamma-ImPyPyIm-beta-Dp (1) and PyPyPyPy-(R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) were synthesized which have in common an Py/Im pair in the terminal position for targeting C x G but differ with respect to internal placement of a beta-alanine residue. The equilibrium association constants (Ka) were determined at four DNA sites which differ at a single common position, 5'-TNTACA-3' (N = T, A, G, C). Quantitative DNase I footprint titration experiments reveal that the eight-ring hairpin PyPyPyPy-(R)(H2N)gamma-ImPyPyIm-beta-Dp (1) binds the four binding sites with similar affinities, Ka = 1.3-1.9 x 10(10) M(-1) indicating that there is no preference for the position N. In contrast, a redesigned polyamide PyPyPyPy-(R)(H2N)gamma-ImPy-beta-Im-beta-Dp (2) that places an internal flexible aliphatic beta-alanine to the 5'-side of a key imidazole group bound the match site 5'-TCTACA-3' with high affinity and good sequence discrimination (Ka(match) = 4.9 x 10(10) M(-1) and the single base pair mismatch sites with 5- to 25-fold lower affinity). These results expand the repertoire of sequences targetable by hairpins and emphasize the importance of beta-alanine as a key element for minor groove recognition.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Wang CC,Ellervik U,Dervan PB

doi

10.1016/s0968-0896(00)00282-0

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

653-7

issue

3

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(00)00282-0

journal_volume

9

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • QSAR models for Daphnia toxicity of pesticides based on combinations of topological parameters of molecular structures.

    abstract：:A topological parameter is defined as an integer value of a given local or global invariant of a molecular graph. We examined three types of local graph invariants, the vertex degrees (0EC), the extended connectivity of first order (1EC), and the numbers of paths of length two (P2), as elementary invariants for constr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.11.060

    authors： Toropov AA,Benfenati E

    更新日期：2006-04-15 00:00:00

  • Design, synthesis and biological activity of 3-pyrazine-2-yl-oxazolidin-2-ones as novel, potent and selective inhibitors of mutant isocitrate dehydrogenase 1.

    abstract：:Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG) generating carbon dioxide and NADPH/NADH. Evidence suggests that the specific mutations in IDH1 are critical to the growth and reproduction of some tumor cells such as gliomas and acute myeloid leukemia,...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.10.009

    authors： Ma T,Zou F,Pusch S,Yang L,Zhu Q,Xu Y,Gu Y,von Deimling A,Zha X

    更新日期：2017-12-15 00:00:00

  • Synthesis, structural investigations and biological evaluation of novel hexahydropyridazine-1-carboximidamides, -carbothioamides and -carbothioimidic acid esters as inducible nitric oxide synthase inhibitors.

    abstract：:Local excess of nitric oxide (NO) has been implicated in beta-cell damage, thus, a possible approach to the treatment of autoimmune IDDM is the selective inhibition of inducible nitric oxide synthase (iNOS). A series of variously substituted hexahydropyridazine-1-carbothioamides, -carbothioimidic acid esters and -carb...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.12.007

    authors： Morgenstern O,Wanka H,Röser I,Steveling A,Kuttler B

    更新日期：2004-03-01 00:00:00

  • Structure-based approach to falcipain-2 inhibitors: synthesis and biological evaluation of 1,6,7-trisubstituted dihydroisoquinolines and isoquinolines.

    abstract：:1,4,7-Trisubstituted isoquinolines were designed, synthesized and evaluated for their inhibition against Plasmodium falciparum cysteine protease falcipain-2. The 1-benzyloxyphenyl-dihydroisoquinoline and -isoquinoline derivatives were found to exhibit better activity against falcipain-2 than their corresponding 1-hydr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00117-2

    authors： Batra S,Sabnis YA,Rosenthal PJ,Avery MA

    更新日期：2003-05-15 00:00:00

  • QSAR by LFER model of HIV protease inhibitor mannitol derivatives using FA-MLR, PCRA, and PLS techniques.

    abstract：:The present quantitative structure-activity relationship (QSAR) study attempts to explore the structural and physicochemical requirements of mannitol derivatives for HIV protease inhibitory activity using linear free energy related model of Hansch. QSAR models have been developed using electronic (Hammett sigma), hydr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.09.022

    authors： Leonard JT,Roy K

    更新日期：2006-02-15 00:00:00

  • Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands.

    abstract：:Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.05.045

    authors： Takamura Y,Shibahara O,Watanabe M,Fujihara M,Yamada S,Akehi M,Sasaki T,Hirano H,Kakuta H

    更新日期：2019-07-15 00:00:00

  • Novel DNA-directed alkylating agents: design, synthesis and potent antitumor effect of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker.

    abstract：:A series of phenyl N-mustard-9-anilinoacridine conjugates via a carbamate or carbonate linker was synthesized for antitumor evaluation. The carbamate or carbonate linker is able to lower the reactivity of the phenyl N-mustard pharmacophore and thus, these conjugates are rather chemically stable. The in vitro studies r...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.12.022

    authors： Kapuriya N,Kapuriya K,Dong H,Zhang X,Chou TC,Chen YT,Lee TC,Lee WC,Tsai TH,Naliapara Y,Su TL

    更新日期：2009-02-01 00:00:00

  • Cyclopentitol as a scaffold for a natural product-like compound library for drug discovery.

    abstract：:A concise and efficient synthesis of cyclopentitols as a scaffold for a two-dimensional compound library for drug discovery is described. Starting from d-mannose, the key steps are Wittig olefination and ring-closing metathesis (RCM) followed by a [3,3]-sigmatropic Overmann rearrangement to form an sp(3)-rich, natural...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.01.040

    authors： Padwal JD,Filippov DV,Narhe BD,Aertssen S,Beuving RJ,Benningshof JC,van der Marel GA,Overkleeft HS,van der Stelt M

    更新日期：2015-06-01 00:00:00

  • Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20.

    abstract：:The preparation and biological evaluation of a novel series of dimeric camptothecin derivatives are described. All the new compounds showed a significant ability to inhibit human tumor cell growth with IC(50) values ranging from 0.03 to 12.2 μM. The interference with the activity of the nuclear enzymes topoisomerases ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.09.069

    authors： Riva E,Comi D,Borrelli S,Colombo F,Danieli B,Borlak J,Evensen L,Lorens JB,Fontana G,Gia OM,Via LD,Passarella D

    更新日期：2010-12-15 00:00:00

  • Effect of single pyrrole replacement with β-alanine on DNA binding affinity and sequence specificity of hairpin pyrrole/imidazole polyamides targeting 5'-GCGC-3'.

    abstract：:N-Methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that can recognize predetermined DNA sequences with high sequence specificity. As many eukaryotic promoter regions contain highly GC-rich sequences, it is valuable to synthesize and characterize Py-Im polyamides that recognize GC-rich m...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.06.005

    authors： Han YW,Kashiwazaki G,Morinaga H,Matsumoto T,Hashiya K,Bando T,Harada Y,Sugiyama H

    更新日期：2013-09-01 00:00:00

  • Conjugation of a 3-(1H-phenanthro[9,10-d]imidazol-2-yl)-1H-indole intercalator to a triplex oligonucleotide and to a three-way junction.

    abstract：:A new intercalating nucleic acid monomer M comprising a 4-(1-indole)-butane-1,2-diol moiety was synthesized via a classical alkylation reaction of indole-3-carboxaldehyde followed by a condensation reaction with phenanthrene-9,10-dione in the presence of ammonium acetate to form a phenanthroimidazole moiety linked to ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.11.013

    authors： Fatthalla MI,Elkholy YM,Abbas NS,Mandour AH,Jørgensen PT,Bomholt N,Pedersen EB

    更新日期：2012-01-01 00:00:00

  • Synthesis and antitumor activity of 20-O-linked nitrogen-based camptothecin ester derivatives.

    abstract：:A series of nitrogen-based 20S-hydroxyl camptothecin ester derivatives were prepared. 3-Aminopropionate of camptothecin was found more cytotoxic in vitro on several human tumor cell lines than 3-amidopropionate of camptothecin. Ester 16 showed best antitumor activity in vivo and in vitro in all esters we prepared. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.04.023

    authors： Wang CY,Pan XD,Liu HY,Fu ZD,Wei XY,Yang LX

    更新日期：2004-07-01 00:00:00

  • Synthesis and preliminary biological evaluation of O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine as a novel potential PET probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in cancer chemotherapy.

    abstract：:A novel fluorine-18-labeled O6-benzylguanine (O6-BG) derivative, O6-[4-(2-[18F]fluoroethoxymethyl)benzyl]guanine (O6-[18F]FEMBG, [18F]1), has been synthesized for evaluation as a potential positron emission tomography (PET) probe for the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) in cancer chemother...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.05.061

    authors： Wang JQ,Kreklau EL,Bailey BJ,Erickson LC,Zheng QH

    更新日期：2005-10-15 00:00:00

  • Crop plants versus energy plants--on the international food crisis.

    abstract：:The recent price explosion of important agricultural commodities has lead to an international food crisis. The price rise is attributed to fundamental factors, such as the rising demand for dairy and meat products in China and the development of the bioenergy branch as well as on short-term factors such as the behavio...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.11.041

    authors： Schmitz PM,Kavallari A

    更新日期：2009-06-15 00:00:00

  • 4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.

    abstract：:A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.07.040

    authors： Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

    更新日期：2018-08-15 00:00:00

  • Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway.

    abstract：:We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable properties. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory acti...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.001

    authors： Mahindroo N,Connelly MC,Punchihewa C,Yang L,Yan B,Fujii N

    更新日期：2010-07-01 00:00:00

  • Antitumor activity of some natural flavonoids and synthetic derivatives on various human and murine cancer cell lines.

    abstract：:The effect of various natural flavonoids, cinnamic acid derivatives, and a series of synthetic flavones on cell proliferation was evaluated in vitro in a panel of established human and murine tumor cell lines. The most potent antiproliferative agents were caffeic acid n-butyl ester (12) > 2'-nitroflavone (26) > caffei...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.12.021

    authors： Cárdenas M,Marder M,Blank VC,Roguin LP

    更新日期：2006-05-01 00:00:00

  • Design, synthesis and biological evaluation of cycloalkyl arylpyrimidines (CAPYs) as HIV-1 NNRTIs.

    abstract：:A series of 18 cycloalkyl arylpyrimidines (CAPYs) were designed from lead compounds diarylpyrimidines (DAPYs), synthesized and evaluated for in vitro anti-HIV activity. Among them, the compound 1p displayed potent anti-HIV-1 activity against WT HIV-1 with an EC(50) value of 0.055 μM and a selectivity index (SI) >7290....

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.10.002

    authors： Gu SX,Yang SQ,He QQ,Ma XD,Chen FE,Dai HF,Clercq ED,Balzarini J,Pannecouque C

    更新日期：2011-12-01 00:00:00

  • Screening helix-threading peptides for RNA binding using a thiazole orange displacement assay.

    abstract：:The fluorescent intercalator displacement assay using thiazole orange has been adapted to the study of RNA-binding helix-threading peptides (HTPs). This assay is highly sensitive with HTP-binding RNAs and provides binding affinity data in good agreement with quantitative ribonuclease footprinting without the need for ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.08.066

    authors： Krishnamurthy M,Schirle NT,Beal PA

    更新日期：2008-10-01 00:00:00

  • ortho-Halogen naphthaleins as specific inhibitors of Lactobacillus casei thymidylate synthase. Conformational properties and biological activity.

    abstract：:Thymidylate synthase (TS) (EC 2.1.1.45), an enzyme involved in the DNA synthesis of both prokaryotic and eukaryotic cells, is a potential target for the development of anticancer and antinfective agents. Recently, we described a series of phthalein and naphthalein derivatives as TS inhibitors. These compounds have str...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00541-2

    authors： Ghelli S,Rinaldi M,Barlocco D,Gelain A,Pecorari P,Tondi D,Rastelli G,Costi MP

    更新日期：2003-03-20 00:00:00

  • Synthetic strategies toward carbocyclic purine-pyrimidine hybrid nucleosides.

    abstract：:The blending of key structural features from the purine and pyrimidine nucleobase scaffolds gives rise to a new class of hybrid nucleosides. The purine-pyrimidine hybrid nucleosides can be viewed as either N-3 ribosylated purines or 5,6-disubstituted pyrimidines, thus recognition by both purine- and pyrimidine-metabol...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.06.039

    authors： Sadler JM,Mosley SL,Dorgan KM,Zhou ZS,Seley-Radtke KL

    更新日期：2009-08-01 00:00:00

  • Reversed isoniazids: Design, synthesis and evaluation against Mycobacterium tuberculosis.

    abstract：:Novel reversed isoniazid (RINH) agents were synthesized by covalently linking isoniazid with various efflux pump inhibitor (EPI) cores and their structural motifs. These RINH agents were then evaluated for anti-mycobacterial activity against sensitive, isoniazid mono-resistant and MDR clinical isolates of M. tuberculo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.12.047

    authors： Kumar M,Singh K,Ngwane AH,Hamzabegovic F,Abate G,Baker B,Wiid I,Hoft DF,Ruminski P,Chibale K

    更新日期：2018-02-15 00:00:00

  • Comprehensive structure-activity-relationship of azaindoles as highly potent FLT3 inhibitors.

    abstract：:Acute myeloid leukemia (AML) is characterized by fast progression and low survival rates, in which Fms-like tyrosine kinase 3 (FLT3) receptor mutations have been identified as a driver mutation in cancer progression in a subgroup of AML patients. Clinical trials have shown emergence of drug resistant mutants, emphasiz...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.01.006

    authors： Grimm SH,Gagestein B,Keijzer JF,Liu N,Wijdeven RH,Lenselink EB,Tuin AW,van den Nieuwendijk AMCH,van Westen GJP,van Boeckel CAA,Overkleeft HS,Neefjes J,van der Stelt M

    更新日期：2019-03-01 00:00:00

  • Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies.

    abstract：:Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC 4.2.1.1) transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.07.066

    authors： Mollica A,Costante R,Akdemir A,Carradori S,Stefanucci A,Macedonio G,Ceruso M,Supuran CT

    更新日期：2015-09-01 00:00:00

  • Use of a deoxynojirimycin-fluorophore conjugate as a cell-specific imaging probe targeting α-glucosidase on cell membranes.

    abstract：:Molecules designed for cell-specific imaging were studied, taking advantage of an enzyme-inhibitor interaction. 1-Deoxynojirimycin (DNJ) can be actively captured by cells which express the surface membrane protein α-glucosidase. New probes composed of DNJ for recognition linked to a fluorophore signal portion were pre...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.01.032

    authors： Hatano A,Kanno Y,Kondo Y,Sunaga Y,Umezawa H,Fukui K

    更新日期：2019-03-01 00:00:00

  • Chemiluminescence flow sensor for berberine with immobilized reagents.

    abstract：:A sensitive chemiluminescence (CL) sensor for berberine combined with flow-injection (FI) technology is described. The analytical reagents involved in the CL reaction, including luminol and potassium ferricyanide, were both immobilized on an anion-exchange resin column. While a volume of sodium phosphate was passed th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00069-4

    authors： Song Z,Zhao T,Wang L,Xiao Z

    更新日期：2001-07-01 00:00:00

  • Synthesis of curcumin mimics with multidrug resistance reversal activities.

    abstract：:In order to discover novel multidrug resistance (MDR) reversal agents for efficient cancer chemotherapy, the unsymmetrical curcumin mimics with various amide moieties (6-19) were synthesized and evaluated their MDR reversal activities in MDR cell line KBV20C. Among the tested compounds, 13, 16, and 17 showed potent MD...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.02.012

    authors： Um Y,Cho S,Woo HB,Kim YK,Kim H,Ham J,Kim SN,Ahn CM,Lee S

    更新日期：2008-04-01 00:00:00

  • Inhibitors of human tyrosyl-DNA phospodiesterase (hTdp1) developed by virtual screening using ligand-based pharmacophores.

    abstract：:Human tyrosyl-DNA phosphodiesterase (hTdp1) inhibitors have become a major area of drug research and structure-based design since they have been shown to work synergistically with camptothecin (CPT) and selectively in cancer cells. The pharmacophore features of 14 hTdp1 inhibitors were used as a filter to screen the C...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.11.008

    authors： Weidlich IE,Dexheimer T,Marchand C,Antony S,Pommier Y,Nicklaus MC

    更新日期：2010-01-01 00:00:00

  • Design and synthesis of 8-hydroxyquinoline-based radioprotective agents.

    abstract：:In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.06.017

    authors： Ariyasu S,Sawa A,Morita A,Hanaya K,Hoshi M,Takahashi I,Wang B,Aoki S

    更新日期：2014-08-01 00:00:00

  • Syntheses, activity and modeling studies of 3- and 4-(sulfo- and sulfonamidoalkyl)pyridine and piperidine-2-carboxylic acid derivatives as analogs of NMDA receptor antagonists.

    abstract：:A series of 3- and 4-(sulfo- and sulfonamidoalkyl)pyridine and piperidine-2-carboxylic acid derivatives as analogs of NMDA receptor antagonists was prepared. Affinity for the NMDA receptor was determined by binding assays using the specific radioligand [3H] (2SR,4RS)-4-(phosphonomethyl)piperidine-2-carboxylic acid (CG...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0968-0896(95)00087-w

    authors： el Hadri A,Maldivi P,Leclerc G,Rocher JP

    更新日期：1995-09-01 00:00:00