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


: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 receptors suggested that the receptor-bound conformation comprises two alpha-helical segments between residues 11-21 and 23-34. It is notable that the N-terminal alpha-helix is extended to Thr(11), and that Gly(22) plays a pivotal role in arranging the two alpha-helices. Based on these findings, a highly potent bicyclic GLP-1 analogue was synthesized which is the most conformationally constrained GLP-1 analogue reported to date.


Bioorg Med Chem


Murage EN,Schroeder JC,Beinborn M,Ahn JM




Has Abstract


2008-12-01 00:00:00














  • 4-(Anilino)pyrrole-2-carboxamides: Novel non-steroidal/non-anilide type androgen antagonists effective upon human prostate tumor LNCaP cells with mutated nuclear androgen receptor.

    abstract::Various 4-(anilino)pyrrole-2-carboxamides were designed and synthesized as novel androgen receptor (AR) antagonists without steroidal or anilide structure, based on our strategy for developing full antagonists of nuclear receptors. Introduction of a bulky N-alkyl group, such as a cyclohexylmethyl or benzyl group, incr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wakabayashi K,Imai K,Miyachi H,Hashimoto Y,Tanatani A

    更新日期:2008-07-15 00:00:00

  • Investigation of platelet aggregation inhibitory activity by phenyl amides and esters of piperidinecarboxylic acids.

    abstract::A series of anilides and phenyl esters of piperidine-3-carboxylic acid (nipecotic acid) were synthesized and tested for the ability to inhibit aggregation of human platelet rich-plasma triggered by adenosine 5'-diphosphate (ADP) and adrenaline. As a rule, amides were about two times more active than the corresponding ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: de Candia M,Summo L,Carrieri A,Altomare C,Nardecchia A,Cellamare S,Carotti A

    更新日期:2003-04-03 00:00:00

  • Benzenepolycarboxylic acids with potential anti-hemorrhagic properties and structure-activity relationships.

    abstract::Previously, we reported the structural requirements of the cinnamic acid relatives for inhibition of snake venom hemorrhagic action. In the present study, we examined the effect of benzenepolycarboxylic acids and substituted benzoic acids against Protobothropsflavoviridis venom-induced hemorrhage. Pyromellitic acid (1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Aung HT,Nikai T,Niwa M,Takaya Y

    更新日期:2011-12-01 00:00:00

  • Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    abstract::We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tsuji T,Suzuki K,Nakamura T,Goto T,Sekiguchi Y,Ikeda T,Fukuda T,Takemoto T,Mizuno Y,Kimura T,Kawase Y,Nara F,Kagari T,Shimozato T,Yahara C,Inaba S,Honda T,Izumi T,Tamura M,Nishi T

    更新日期:2014-08-01 00:00:00

  • Pleuromutilins. Part 1. The identification of novel mutilin 14-carbamates.

    abstract::A novel series of mutilin 14-carbamates has been discovered as a result of structure-activity studies on the naturally occurring antibiotic pleuromutilin (1). In particular, the 4-methoxybenzoylcarbamate, SB-222734 (15o) displays potent antibacterial activity against a number of bacterial pathogens which are resistant...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brooks G,Burgess W,Colthurst D,Hinks JD,Hunt E,Pearson MJ,Shea B,Takle AK,Wilson JM,Woodnutt G

    更新日期:2001-05-01 00:00:00

  • The 3-D QSAR study of anticancer 1-N-substituted imidazo- and pyrrolo-quinoline-4,9-dione derivatives by CoMFA and CoMSIA.

    abstract::The 3-D QSAR analysis with new imidazo- and pyrrolo-quinolinedione derivatives was conducted by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). When crossvalidation value (q(2)) is 0.844 at four components, the Pearson correlation coefficient (r(2)) of the C...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Suh ME,Kang MJ,Park SY

    更新日期:2001-11-01 00:00:00

  • Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster.

    abstract::Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tatsumi T,Awahara C,Naka H,Aimoto S,Konno H,Nosaka K,Akaji K

    更新日期:2010-04-01 00:00:00

  • Synthesis of amino acid derived seven-membered lactams by RCM and their evaluation against HIV protease.

    abstract::A versatile synthesis of hydroxylated and epoxy 1-azepin 2-ones substituted at N1, C-3 and C-4 or C-7 has been developed. The sequence involves ring-closing metathesis of an amino acid derived diene amide, followed by either epoxidation or dihydroxylation, of the resulting alkene. Assay of the product epoxides (10, 18...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zaman S,Campaner P,Abell AD

    更新日期:2006-12-15 00:00:00

  • Piperine analogs as potent Staphylococcus aureus NorA efflux pump inhibitors.

    abstract::Based on our recent findings that piperine is a potent Staphylococcus aureus NorA efflux pump inhibitor (EPI), 38 piperine analogs were synthesized and bioevaluated for their EPI activity. Twenty-five of them were found active with potentiating activity equivalent or more than known EPIs like reserpine, carsonic acid ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sangwan PL,Koul JL,Koul S,Reddy MV,Thota N,Khan IA,Kumar A,Kalia NP,Qazi GN

    更新日期:2008-11-15 00:00:00

  • Molecular docking identifies the binding of 3-chloropyridine moieties specifically to the S1 pocket of SARS-CoV Mpro.

    abstract::The 3C-like main proteinase of the severe acute respiratory syndrome (SARS) coronavirus, SARS-CoV M(pro), is widely considered to be a major drug target for the development of anti-SARS treatment. Based on the chemical structure of a lead compound from a previous screening, we have designed and synthesized a number of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Niu C,Yin J,Zhang J,Vederas JC,James MN

    更新日期:2008-01-01 00:00:00

  • The selective quantification of iron by hexadentate fluorescent probes.

    abstract::The synthesis of four hexadentate fluorescent probes is described, where the fluorescent moiety is based on either coumarin or fluorescein and the chelating moiety is based on either 3-hydroxypyridin-4-one or 3-hydroxypyran-4-one. The fluorescence is quenched when the probe chelating moieties bind iron. The probes wer...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ma YM,Hider RC

    更新日期:2009-12-01 00:00:00

  • Baylis-Hillman reaction assisted parallel synthesis of 3,5-disubstituted isoxazoles and their in vivo bioevaluation as antithrombotic agents.

    abstract::The solution-phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detaile...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Batra S,Roy AK,Patra A,Bhaduri AP,Surin WR,Raghavan SA,Sharma P,Kapoor K,Dikshit M

    更新日期:2004-05-01 00:00:00

  • Insect neuropeptides: structures, chemical modifications and potential for insect control.

    abstract::Insect neuropeptides are involved in almost all physiological processes in insects, such as diuresis, ecdysis, pheromone biosynthesis and control of muscle activity. Thus, these small peptide hormones and their receptors are promising targets for a novel generation of selective and non-neurotoxic insecticides. However...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Scherkenbeck J,Zdobinsky T

    更新日期:2009-06-15 00:00:00

  • Responsive Mn(II) complexes for potential applications in diagnostic Magnetic Resonance Imaging.

    abstract::The investigation of new Mn(II)-based MRI/Molecular Imaging probes responsive to the enzyme tyrosinase for potential diagnostic applications is herein described. The expression of the enzyme tyrosinase, an oxidoreductase, is up-regulated in melanoma cancer cells. Three novel ligands (L(1), L(2) and L(3)) were designed...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rolla GA,Tei L,Fekete M,Arena F,Gianolio E,Botta M

    更新日期:2011-02-01 00:00:00

  • 2-(2-Bromophenyl)-formononetin and 2-heptyl-formononetin are PPARγ partial agonists and reduce lipid accumulation in 3T3-L1 adipocytes.

    abstract::Isoflavones are bioactive compounds that have been shown to decrease lipid accumulation in vitro. However, the knowledge of the isoflavone formononetin is limited. The aim of the study was to assess the effects of formononetin and its two synthetic analogues, 2-(2-bromophenyl)-formononetin and 2-heptyl-formononetin, o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Andersen C,Kotowska D,Tortzen CG,Kristiansen K,Nielsen J,Petersen RK

    更新日期:2014-11-01 00:00:00

  • A colormetric assay for catechol-O-methyltransferase.

    abstract::A series of catechol diazo dyes were synthesized and tested as substrates for the enzyme catechol-O-methyltransferase (COMT) with the aim of developing a sensitive HPLC assay method using visible wavelength light detection. A method was developed which allowed for the determination of the two regioisomeric methylated ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bailey K,Cowling R,Tan EW,Webb D

    更新日期:2004-02-01 00:00:00

  • Synthesis, antitumor activity and structure-activity studies of novel pyridoxine-based bioisosteric analogs of estradiol.

    abstract::A new efficient approach to the synthesis of 6-alkenyl substituted pyridoxine derivatives has been developed. A series of 31 novel alkenyl pyridoxine derivatives, stilbene-based bioisosteric analogs of estradiol, were synthesized. In vitro cytotoxicity of the obtained compounds against MCF-7 (ER+) breast cancer tumor ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pugachev MV,Pavelyev RS,Nguyen TNT,Gabbasova RR,Bulatov TM,Iksanova AG,Aljondi B,Bondar OV,Grishaev DY,Yamaleeva ZR,Kataeva ON,Nikishova TV,Balakin KV,Shtyrlin YG

    更新日期:2021-01-15 00:00:00

  • Nucleotide analogues containing 2-oxa-bicyclo[2.2.1]heptane and l-alpha-threofuranosyl ring systems: interactions with P2Y receptors.

    abstract::The ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of the P2Y(1) receptor has been successfully substituted with a rigid methanocarba ring system, leading to the conclusion that the North (N) ring conformation is preferred in receptor binding. Similarly, at P2Y(2) and P2Y(4) receptors, nucleotides ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ohno M,Costanzi S,Kim HS,Kempeneers V,Vastmans K,Herdewijn P,Maddileti S,Gao ZG,Harden TK,Jacobson KA

    更新日期:2004-11-01 00:00:00

  • Targeting the Warburg Effect in cancer; relationships for 2-arylpyridazinones as inhibitors of the key glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3).

    abstract::High-throughput screening of a small-molecule library identified a 5-triazolo-2-arylpyridazinone as a novel inhibitor of the important glycolytic enzyme 6-phosphofructo-2-kinase/2,6-bisphosphatase 3 (PFKFB3). Such inhibitors are of interest due to PFKFB3's control of the important glycolytic pathway used by cancer cel...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brooke DG,van Dam EM,Watts CK,Khoury A,Dziadek MA,Brooks H,Graham LJ,Flanagan JU,Denny WA

    更新日期:2014-02-01 00:00:00

  • SAR studies of acidic dual γ-secretase/PPARγ modulators.

    abstract::A novel set of dual γ-secretase/PPARγ modulators characterized by a 2-benzyl hexanoic acid scaffold is presented. Synthetic efforts were focused on the variation of the substitution pattern of the central benzene. Finally, we obtained a new class of 2,5-disubstituted 2-benzylidene hexanoic acid derivatives, which act ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hieke M,Ness J,Steri R,Greiner C,Werz O,Schubert-Zsilavecz M,Weggen S,Zettl H

    更新日期:2011-09-15 00:00:00

  • Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase.

    abstract::Structure-activity relationships of amide-phosphonate derivatives as inhibitors of the human soluble epoxide hydrolase (sEH) were investigated. First, a series of alkyl or aryl groups were substituted on the carbon alpha to the phosphonate function in amide compounds to see whether substituted phosphonates can act as ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kim IH,Park YK,Nishiwaki H,Hammock BD,Nishi K

    更新日期:2015-11-15 00:00:00

  • Synthesis and antitumor evaluation of a novel series of triaminotriazine derivatives.

    abstract::A series of triaminotriazine derivatives (compounds 5a-f, 6a-x, and 7a-g) was designed, synthesized, and evaluated for their inhibition activities to colorectal cancer (CRC) cell lines (HCT-116 and HT-29). Most of the synthesized compounds demonstrated moderate anti-proliferatory effects on both HCT-116 and HT-29 cell...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zheng M,Xu C,Ma J,Sun Y,Du F,Liu H,Lin L,Li C,Ding J,Chen K,Jiang H

    更新日期:2007-02-15 00:00:00

  • Synthesis of hydrolysis-resistant pyridoxal 5'-phosphate analogs and their biochemical and X-ray crystallographic characterization with the pyridoxal phosphatase chronophin.

    abstract::A set of phosphonic acid derivatives (1-4) of pyridoxal 5'-phosphate (PLP) was synthesized and characterized biochemically using purified murine pyridoxal phosphatase (PDXP), also known as chronophin. The most promising compound 1 displayed primarily competitive PDXP inhibitory activity with an IC50 value of 79μM, whi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Knobloch G,Jabari N,Stadlbauer S,Schindelin H,Köhn M,Gohla A

    更新日期:2015-06-15 00:00:00

  • Transition state analogue inhibitors of protozoan nucleoside hydrolases.

    abstract::Protozoan parasites are unable to synthesize purines de novo and must rely on purine salvage pathways for their requirements. Nucleoside hydrolases, which are not found in mammals, function as key enzymes in purine salvage in protozoa. Inhibition of these enzymes may disrupt purine supply and specific inhibitors are p...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Furneaux RH,Schramm VL,Tyler PC

    更新日期:1999-11-01 00:00:00

  • Structure-based discovery of small molecule hepsin and HGFA protease inhibitors: Evaluation of potency and selectivity derived from distinct binding pockets.

    abstract::Hepatocyte growth factor activator (HGFA), matriptase and hepsin are all S1 trypsin-like serine endopeptidases. HGFA is a plasma protease while hepsin and matriptase are type II transmembrane proteases (TTSPs). Upregulated expression and activity of all three proteases is associated with aberrant cancer cell signaling...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Franco FM,Jones DE,Harris PK,Han Z,Wildman SA,Jarvis CM,Janetka JW

    更新日期:2015-05-15 00:00:00

  • Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.

    abstract::Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDP...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Goetz DB,Varney ML,Wiemer DF,Holstein SA

    更新日期:2020-08-15 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


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

    更新日期:2007-02-15 00:00:00

  • Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase.

    abstract::The purpose of the present study was to discover the extent of contribution to antityrosinase activity by adding hydroxy substituted benzoic acid, cinnamic acid and piperazine residues to vanillin. The study showed the transformation of vanillin into esters as shown in (4a-4d), (6a-6b), and (8a-8b). In addition, the r...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ashraf Z,Rafiq M,Seo SY,Babar MM,Zaidi NU

    更新日期:2015-09-01 00:00:00

  • Design, synthesis and pharmacological evaluation of novel naphthalenic derivatives as selective MT(1) melatoninergic ligands.

    abstract::Novel heterodimer analogues of melatonin were synthesized, when agomelatine (1) and various aryl units are linked via a linear alkyl chain through the methoxy group. The compounds were tested for their actions at melatonin receptors. Several of these ligands are MT(1)-selective with nanomolar or subnanomolar affinity....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mésangeau C,Pérès B,Descamps-François C,Chavatte P,Audinot V,Coumailleau S,Boutin JA,Delagrange P,Bennejean C,Renard P,Caignard DH,Berthelot P,Yous S

    更新日期:2010-05-15 00:00:00

  • Impact of stereochemistry on the biological activity of novel oleandomycin derivatives.

    abstract::A set of 8-methylene-, 8-methyl-, and 8-methyl-9-dihydro-oleandomycin derivatives having different combinations of stereochemistries at positions C-8 and/or C-9 have been prepared in a chemoselective and stereoselective manner and tested in vitro for antibacterial activity and inhibition of IL-6 production. Configurat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bauer J,Vine M,Corić I,Bosnar M,Pašalić I,Turkalj G,Lazarevski G,Culić O,Kragol G

    更新日期:2012-04-01 00:00:00