Site-specific effect of polar functional group-modification in lipids of TLR2 ligands for modulating the ligand immunostimulatory activity.


:Toll-like receptor 2 (TLR2), a member of the TLR innate immune receptor family, recognizes lipoproteins from bacteria and modulates the immune response by inducing the expression of various cytokines. TLR2 has a large hydrophobic pocket that recognizes long fatty acyl groups on TLR2 ligands. However, few studies have focused on the property of the hydrophobic TLR2 pocket. Based on the X-ray crystal structure of TLR2, small polar regions were found in the hydrophobic TLR2 pocket. Interactions between the polar residues and ligands were explored here by designing and synthesizing a Pam2CSK4 derivative of the TLR2 ligands, containing an amide group within the lipid moiety. We evaluated the binding affinities and immunomodulatory activities of these ligands. Results suggested that the amide groups in the lipid chain interacted with the polar residues in the hydrophobic lipid-binding pocket of TLR2.


Bioorg Med Chem Lett


Arai Y,Inuki S,Fujimoto Y




Has Abstract


2018-05-15 00:00:00














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    abstract::A series of 6-hydroxy-7-methoxy-4-chromanone- (2a-e) and chroman-2-carboxamides (3a-e) were synthesized and their antioxidant activities were evaluated. While compounds 2a-e were less active, compounds 3a-e exhibited more potent inhibition of lipid peroxidation initiated by Fe(2+) and ascorbic acid in rat brain homoge...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lee H,Lee K,Jung JK,Cho J,Theodorakis EA

    更新日期:2005-06-02 00:00:00

  • Bis-pyridiumaldoxime reactivators connected with CH2O(CH2)n OCH2 linkers between pyridinium rings and their reactivity against VX.

    abstract::New bis-pyridinium oxime reactivators connected with CH2O(CH2)n OCH2 linkers between two pyridinium rings were designed and synthesized, and their reactivation potency was evaluated for AChE inhibited by organophosphorus VX agent. Among the prepared compounds, 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichlor...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Oh KA,Yang GY,Jun D,Kuca K,Jung YS

    更新日期:2006-09-15 00:00:00

  • Diaryl piperidines as CB1 receptor antagonists.

    abstract::The syntheses and SAR investigations of novel CB(1) receptor antagonists based on a 1,2-diaryl piperidine core have been described. Optimization of this core afforded a compound with robust in vivo potency by reducing food intake in a mouse DIO model. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Scott JD,Li SW,Wang H,Xia Y,Jayne CL,Miller MW,Duffy RA,Boykow GC,Kowalski TJ,Spar BD,Stamford AW,Chackalamannil S,Lachowicz JE,Greenlee WJ

    更新日期:2010-02-01 00:00:00

  • Discovery of a novel class of selective human CB1 inverse agonists.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Foloppe N,Allen NH,Bentley CH,Brooks TD,Kennett G,Knight AR,Leonardi S,Misra A,Monck NJ,Sellwood DM

    更新日期:2008-02-01 00:00:00

  • Synthesis and cytotoxic evaluation of novel paraconic acid analogs.

    abstract::A novel class of 2,3-tri- and tetrasubstituted γ-butyrolactones analogous to paraconic acids has been synthesized in one step using a straightforward three-component reaction among aryl bromides, dimethyl itaconate and carbonyl compounds. The in vitro cytotoxic activity of representative compounds has been evaluated a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Le Floch C,Le Gall E,Léonel E,Martens T,Cresteil T

    更新日期:2011-12-01 00:00:00

  • Potent and selective CC-chemokine receptor-2 (CCR2) antagonists as a potential treatment for asthma.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lagu B,Gerchak C,Pan M,Hou C,Singer M,Malaviya R,Matheis M,Olini G,Cavender D,Wachter M

    更新日期:2007-08-01 00:00:00

  • Synthesis and antibacterial activity of C2-fluoro, C6-carbamate ketolides, and their C9-oximes.

    abstract::Novel C6-carbamate ketolides with C2-fluorination and C9-oximation have been synthesized. The best compounds in this series displayed MIC values of 0.03-0.12 microg/mL against streptococci containing erm and mef resistance determinants and 2-4 microg/mL against Haemophilus influenzae. Several compounds also showed mea...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Xu X,Henninger T,Abbanat D,Bush K,Foleno B,Hilliard J,Macielag M

    更新日期:2005-02-15 00:00:00

  • Synthesis and biological evaluation of new symmetric curcumin derivatives.

    abstract::A series of novel curcumin bisacetamides aiming of enriching their biological activities have been synthesized. The synthesized compounds were screened for their in vitro antioxidant, anti-inflammatory and cytotoxic activities. All the compounds exhibited potent to good anti-inflammatory, antioxidant and noteworthy cy...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sribalan R,Kirubavathi M,Banuppriya G,Padmini V

    更新日期:2015-10-01 00:00:00

  • Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064.

    abstract::Starting from the known FXR agonist GW 4064 1a, a series of alternately 3,5-substituted isoxazoles was prepared. Several of these analogs were potent full FXR agonists. A subset of this series, with a tether between the isoxazole ring and the 3-position aryl substituent, were equipotent FXR agonists to GW 4064 1a, wit...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bass JY,Caldwell RD,Caravella JA,Chen L,Creech KL,Deaton DN,Madauss KP,Marr HB,McFadyen RB,Miller AB,Parks DJ,Todd D,Williams SP,Wisely GB

    更新日期:2009-06-01 00:00:00

  • Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286.

    abstract::The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

    更新日期:2010-12-15 00:00:00

  • Inhibition of human cytomegalovirus protease N(o) with monocyclic beta-lactams.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Déziel R,Malenfant E

    更新日期:1998-06-02 00:00:00

  • An inhibitor-like binding mode of a carbonic anhydrase activator within the active site of isoform II.

    abstract::The 2,4,6-trimethylpyridinium derivative of histamine is an effective activator of the zinc enzyme carbonic anhydrase (CA, EC However, unlike other CA activators, which bind at the entrance of the active site cavity, an X-ray crystal structure of hCA II in complex with the 1-[2-(1H-imidazol-4-yl)-ethyl]-2,4,...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Dave K,Ilies MA,Scozzafava A,Temperini C,Vullo D,Supuran CT

    更新日期:2011-05-01 00:00:00

  • Rhodanine-3-acetic acid derivatives as inhibitors of fungal protein mannosyl transferase 1 (PMT1).

    abstract::The first inhibitors of fungal protein: mannosyl transferase 1 (PMT1) are described. They are based upon rhodanine-3-acetic acid and several compounds have been identified, for example, 5-[[3-(1-phenylethoxy)-4-(2-phenylethoxy)phenyl]methylene]-4-oxo-2-thioxo-3-thiazolidineacetic acid (5a), which inhibit Candida albic...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Orchard MG,Neuss JC,Galley CM,Carr A,Porter DW,Smith P,Scopes DI,Haydon D,Vousden K,Stubberfield CR,Young K,Page M

    更新日期:2004-08-02 00:00:00

  • Structural measurements and cell line studies of the copper-PEG-Rifampicin complex against Mycobacterium tuberculosis.

    abstract::The bacterium responsible for tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used t...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Manning T,Mikula R,Wylie G,Phillips D,Jarvis J,Zhang F

    更新日期:2015-02-01 00:00:00

  • Aromatic phosphonates inhibit the lysophospholipase D activity of autotaxin.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Jiang G,Madan D,Prestwich GD

    更新日期:2011-09-01 00:00:00

  • Syntheses of potent Leu-enkephalin analogs possessing beta-hydroxy-alpha,alpha-disubstituted-alpha-amino acid and their characterization to opioid receptors.

    abstract::Novel Leu-enkephalin (Leu-Enk) (1) analogs possessing various types of alpha-substituted serine instead of its glycine residue in the position 2 were synthesized via an efficient O,N-migration method. The binding characteristics of the synthetic analogs using Chinese hamster ovary (CHO) cells expressed cloned rat mu-,...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Horikawa M,Shigeri Y,Yumoto N,Yoshikawa S,Nakajima T,Ohfune Y

    更新日期:1998-08-04 00:00:00

  • The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist.

    abstract::The 5-HT3 receptor antagonist tropisetron (ICS 205-930) was found to be a potent and selective partial agonist at alpha7 nicotinic receptors. Two other 5-HT3 receptor antagonists, ondansetron and LY-278,584, were found to lack high affinity at the alpha7 nicotinic receptor. Quinuclidine analogues (1 and 2) of tropiset...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Macor JE,Gurley D,Lanthorn T,Loch J,Mack RA,Mullen G,Tran O,Wright N,Gordon JC

    更新日期:2001-02-12 00:00:00

  • Fluorescence detection of serum albumin with a turnover-based sensor utilizing Kemp elimination reaction.

    abstract::The Kemp elimination reaction is a well-known chemical reaction that is facilitated on a protein surface microenvironment, and in particular is highly accelerated in a unique binding pocket of serum albumin. We have designed and synthesized a fluorescently activatable coumarin derivative with a benzisoxazole scaffold ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sakamoto S,Komatsu T,Ueno T,Hanaoka K,Urano Y

    更新日期:2017-08-01 00:00:00

  • Effective molarity in a nucleic acid-controlled reaction.

    abstract::Positioning of reactive functional groups within a DNA duplex can enable chemical reactions that otherwise would not occur to an appreciable extent. However, few studies have quantitatively defined the extent to which the enforced proximity of reaction partners in duplex DNA can favor chemical processes. Here, we meas...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Catalano MJ,Price NE,Gates KS

    更新日期:2016-06-01 00:00:00

  • Stereoselective synthesis of a novel 2-aza-7-oxabicyclo[3.3.0]octane as neurokinin-1 receptor antagonist.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Shishido Y,Ito F,Morita H,Ikunaka M

    更新日期:2007-12-15 00:00:00

  • Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors.

    abstract::Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous amide substituents have been identified as potent PDE3B subtype selective inhibitors. Dihydropyridazinone 8a (PDE3B IC(50)=0.19 nM, 3A IC(50)=1.3 nM) was selected for in vivo evaluation of lipolysis induction, metabolic rate increase, and ca...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Edmondson SD,Mastracchio A,He J,Chung CC,Forrest MJ,Hofsess S,MacIntyre E,Metzger J,O'Connor N,Patel K,Tong X,Tota MR,Van der Ploeg LH,Varnerin JP,Fisher MH,Wyvratt MJ,Weber AE,Parmee ER

    更新日期:2003-11-17 00:00:00

  • Synthesis and SAR of azalide 3,6-ketal aromatic derivatives as potent Gram-positive and Gram-negative antibacterial agents.

    abstract::3,6-Ketals of 15-membered azalide pseudoaglycones are a novel series of macrolide antibiotics. The aromatic derivatives of the azalide 3,6-ketals demonstrated potent antibacterial activities against both Gram-positive and Gram-negative bacteria. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Cheng H,Dirlam JP,Ziegler CB,Lundy KM,Hayashi SF,Kamicker BJ,Dutra JK,Daniel KL,Santoro SL,George DM,Bertsche CD,Sakya SM,Suarez-Contreras M

    更新日期:2002-09-02 00:00:00

  • A facile route to paclitaxel C-10 carbamates.

    abstract::A general protocol for the synthesis of paclitaxel C-10 carbamates is described. The method entails MeI-mediated activation of 2'-O-TBS-7-O-TES-10-O-deacetyl-paclitaxel-10-O-carbonylimidazole prior to reaction with amines. This method is effective for the synthesis of paclitaxel C-10 derivatives, including bifunctiona...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Ballatore C,Aspland SE,Castillo R,Desharnais J,Eustaquio T,Sun C,Castellino AJ,Smith AB 3rd

    更新日期:2005-05-16 00:00:00

  • Synthesis and biological evaluation of [4-(2-phenylethenesulfonylmethyl)phenyl]-quinazolin-4-yl-amines as orally active anti-cancer agents.

    abstract::A new series of [4-(2-phenylethenesulfonylmethyl)phenyl]quinazolin-4-yl-amines was prepared and tested for its in vitro cytotoxic activity against a panel of 12 human cancer cell lines. Compounds 9, 15, 24 and 31 showed good in vitro activity and were further tested for their in vivo efficacy in the HT-29 human colon ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sharma VM,Adi Seshu KV,Chandra Sekhar V,Madan S,Vishnu B,Babu PA,Vamsee Krishna C,Sreenu J,Ravi Krishna V,Venkateswarlu A,Rajagopal S,Ajaykumar R,Kumar TS

    更新日期:2004-01-05 00:00:00

  • Enzymatic synthesis of monocyclic beta-lactams.

    abstract::An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a beta-lactam ring during the biosynthesis of clavulanic acid, an important beta-lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to b...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Sleeman MC,MacKinnon CH,Hewitson KS,Schofield CJ

    更新日期:2002-02-25 00:00:00

  • In vitro selection of a 3' terminal short protector that stabilizes transcripts to improve the translation efficiency in a wheat germ extract.

    abstract::Wheat cell-free expression systems based on wheat germ extract (WGE) enable us to briefly synthesize various types of proteins in vitro merely by exogenously adding their mRNA templates. Moreover, it is possible to produce larger amounts of protein by thoroughly removing the endosperm, which contains many translation ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 信件


    authors: Ogawa A,Kutsuna A,Takamatsu M,Okuzono T

    更新日期:2019-08-15 00:00:00

  • Synthetic analogs of daidzein, having more potent osteoblast stimulating effect.

    abstract::A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of o...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Yadav DK,Gautam AK,Kureel J,Srivastava K,Sahai M,Singh D,Chattopadhyay N,Maurya R

    更新日期:2011-01-15 00:00:00

  • Thiophene-based vitronectin receptor antagonists.

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Bubenik M,Meerovitch K,Bergeron F,Attardo G,Chan L

    更新日期:2003-02-10 00:00:00

  • 4,4,14 alpha-trimethyl 9 beta,19-cyclo-5 alpha-26-homocholesta-24,26-dien-3 beta-ol: a potent mechanism-based inactivator of delta 24(25)- to delta 25(27)-sterol methyl transferase.

    abstract::The title compound (4A) was synthesized and tested as a mechanism-based inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time-dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact value of 0.30 min-1...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Nes WD,He L,Mangla AT

    更新日期:1998-12-15 00:00:00

  • Synthesis and SAR of potent and orally bioavailable tert-butylpyrrolidine archetype derived melanocortin subtype-4 receptor modulators.

    abstract::Discovery of a series of tert-butyl pyrrolidine derived, potent and orally bioavailable melanocortin receptor subtype-4 (MC4R) selective modulators is disclosed. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Guo L,Ye Z,Ujjainwalla F,Sings HL,Sebhat IK,Huber J,Weinberg DH,Tang R,MacNeil T,Tamvakopoulos C,Peng Q,MacIntyre E,van der Ploeg LH,Goulet MT,Wyvratt MJ,Nargund RP

    更新日期:2008-06-01 00:00:00