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[AzaPhe 4 ]GHRP-6 6Fig. 1. Circular dichroism spectra of [azaPhe 4 ]GHRP-6, [aza-3-indoylgly 4 ]GHRP-6(6), and GHRP-6 in water.The evaluation of the biological activity of azapeptide 6 revealed a 10 fold loss ofbinding affinity towards the CD36 receptor, in spite of exhibiting a CD signaturesuggestive of a turn, with negative maxima at 230 and 190 nm and a positive maximumat 215 nm. Although the indolyl side chain of the Trp 4 residue of the GHRP-6 sequencewas maintained in [aza-3-indoylgly 4 ]GHRP-6, the spacial alignment and conformationalconstraints imposed by this aza-arylglycine residue appear to disfavor binding to theCD36 receptor.AcknowledgmentsThe authors thank the Natural Sciences and Engineering Research Council of Canada andBoehringer Ingelheim for financial support.References1. Gante, J. Synthesis 405 (1989).2. (a) André, F., Boussard, G., Bayeul, D., Didierjean, C., Aubry, A., Marraud, M. J. Peptide Res.49, 556-562 (1997); (b) André, F., Vicherat, A., Boussard, G., Aubry, A., Marraud, M. J. PeptideRes. 50, 372-381 (1997).3. Proulx, C., Lubell, W.D. Org. Lett. 12, 2916-2919 (2010).4. Boeglin, D., Lubell, W.D. J. Comb. Chem. 7, 864-878 (2005).5. Sabatino, D., Proulx, C., Klocek, S., Bourguet, C.B., Boeglin, D., Ong, H., Lubell, W.D. Org.Lett. 11, 3650 (2009).459
<strong>Proceedings</strong> of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010N α -Linked Homodimers of the Kinin B1 ReceptorAntagonist R-715Witold A. Neugebauer 1 , Martin Savard 1 , Klaus Klarskov, andFernand Gobeil JrDepartment of Pharmacology, Université de Sherbrooke, Sherbrooke,J1H 5N4, Québec, Canada; E-mail: witold.neugebauer@usherbrooke.ca (WN);fernand.gobeil@usherbrooke.ca (FG); 1 These authors contributed equally to this workIntroductionThe kinin B1 receptor (B1R) may play an important role in pathological conditions. Wepreviously developed a highly potent and selective kinin B1R antagonist, R-715 (Ac-Lys-[D-βNal 7 , Ile 8 ]desArg 9 -bradykinin) [1,2]. However, R-715 is only partially resistant againstenzyme degradation, which may explain its relatively short half life in vivo. It iscontemplated that covalent peptide dimers may improve stability [3-7], circulating half-lifeand make more potent therapeutics than monomers. With this in mind, we 1) designed andsynthesized on solid phase Nα-linked homodimers of R-715 <strong>com</strong>prising linkers withdifferent acyl-chain lengths such as 6 (adipoyl) (NG2049), 8 (suberyl) (NG2035), 10(sebacoyl) (NG2050) and 12 carbons (dodecanedioyl) (NG2051) and 2) determined theirantagonistic potencies (pA 2 value) using rabbit aortic strip contraction assays.Material and MethodsPeptide synthesis: Peptides (Figure 1) were synthesized using Boc chemistry onABI/Applied Biosystems 430A Peptide Synthesizer starting with Boc-Ile-Merrifield resin.Step by step coupling of Boc amino acids were performed in DCM/1-methyl-2-pyrolidinone using DCC/HOBTas coupling agents. Boc deprotectionwas performed with 64%TFA in DCM. TFA salts wereneutralized with DIPEA inDCM. At the last step, peptideswere bridged at their Nα-Lys 1amino-terminal function withdiacid dichlorides (adipoyl-,suberyl-, sebacoyl- and dodecanedioyl-)in DCM in presence ofDIPEA. Final peptides andprotective group cleavage wereperformed by liquefied anhydrousHF treatment. Peptides salts(with resin) were precipitated inanhydrous ethyl ether, filtered,dissolved in 25% Acetic acidand lyophilized. The crudepeptides were finally purified byC18 column chromatography inacetonitrile gradient in waterwith 0.1% TFA. Peptideidentities were confirmed byMALDI mass spectrometry (seeTable 1) and their chromatographicpurity verified by analyticalHPLC.Fig. 1. Structures of B1R antagonist R-715 homodimers.Organ bath: Rabbit aortas frommale New Zealand rabbits(1.5-2.0 kg) were used. Tissuepreparation and experimental460
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Peptides 2010Tales of PeptidesProce
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Peptides 2010Tales of PeptidesProce
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IntroductionWe had the distinct hon
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Scientific programIn planning the 3
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31 st EUROPEAN PEPTIDE SYMPOSIUMSep
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published by John Wiley & Sons as a
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The Josef Rudinger AwardThis award
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Young Investigators' SymposiumThe y
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xxiv
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Design of Peptidyl-Inhibitors for G
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Synthetic Antifreeze Glycopeptide A
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Synthesis and Oxidative Folding of
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Convergent Syntheses of Huprp106-12
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Bactericidal Activity of Small Beta
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Bradykinin Analogues Acylated on Th
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Antimicrobial Activity of Small 3-(
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Interaction of Curcumin with A-Synu
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Fluorescent and Luminescent Fusion
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Cellular Expression of the Human An
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2D IR Spectroscopy of Oligopeptides
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large, non-redundant subset of prot
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The aberrantly glucosylated peptide
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Table 1. Proline cis/trans ratios o
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Table 1. Yields, UV-vis absorption
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Table 1. Purity of the targeted tri
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processes are blocked. Interestingl
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(tb4 n ,1 m )MTII(tb1 n ,4 m )MTIIF
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Fig. 2. a) Part of the 400 MHz HR-M
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Once printed, the amino acid partic
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A) PSA, few seconds73B) PSA, 45 min
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short β strands. In contrast, nume
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neg. control Cs9-Rhd MM-218Fig. 2.
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Table 1. The general structure of t
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% ID in the liver 1 h p.i.100908070
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Peptidyl phosphoranes were first re
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obtained from the same sardines and
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MccJ25 variants were produced by si
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Fig. 2. Proposed signaling mechanis
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Table 1. mCD4-HS12 antiviral activi
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Proceedings of the 31 st European P
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Subject index(S)-2-(1-adamantyl)gly
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chip 18chiral triazine condensing r
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heat stress 348helical conformation
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O-acyl isopeptide method 112obesity
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SH2-ligands 210short collagen-relat
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Author indexAboye, Teshome Leta 142
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Chi, Hongfang 480Chiche, Laurent 6C
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Geronikaki, Athina 444Gessmann, Ren
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Kostova, Kalina 528Kotzia, Georgia
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Nagata, Koji 162Nagayev, Igor Yu. 5
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Salvarese, Nicola 518Sammet, Benedi
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Vauquelin, Georges 138Veiga, Ana Sa
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