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Table 1. Analytical data and antagonistic activities of dimer derivatives of R-715CompoundLinker(n of Carbons)Calculatedm.w. (Da)protocol for vascular contractility bioassays were performed as described [1,2]. Theapparent affinity of each antagonist was evaluated and expressed in terms of pA 2 (thenegative log of the molar concentration of an antagonist that makes it necessary to doublethe concentration of the agonist desArg 9 -bradykinin needed to elicit the originalsubmaximal response).Results and DiscussionOur results showed that all dimeric analogues of R-715 (Figure 1) were capable of blockingthe contractile responses to the kinin B1R agonist desArg 9 -bradykinin in rabbit aorticstrips, although not to the same extent (Table 1). In comparison with the parent monomerantagonist R-715 (pA 2 : 8.40±0.12), the peptide NG2049 (pA 2 : 8.43±0.17) and NG2035(pA 2 : 8.66±0.19) maintained similar inhibitory effects while peptides NG2050 (pA2:7.69±0.14) and NG2051 (pA 2 : 7.75±0.12) showed reduced potencies. We concluded thatthe optimum length of spacer arms of N-terminal dimeric R-715 analogues for B1Rantagonism is with acyl chains of 6 and 8 carbons, which corresponds to a maximal lengthof 7.5 and 9.8 Å. Further studies are needed to test whether the strategy of R-715dimerization translates to greater potency and long-lasting in vivo activity.AcknowledgmentsM. Savard is a former recipient of a fellowship award from the Fonds de la recherche en santé duQuébec (FRSQ). F. Gobeil is a recipient of a Junior 2 scholarship from the FRSQ, a researcher of theCanada Foundation for Innovation, and a member of the FRSQ-funded Centre de recherche cliniqueÉtienne-Le Bel. Research reported in this study was supported by Institutional funds and a grant fromthe Canadian Institute of Health Research (CIHR).References1. Gobeil, F. jr., et al. Hypertension 28, 833-839 (1996).2. Gobeil, F. jr., et al. Hypertension 33, 823-829 (1999).3. Cheronis, J.C., et al. J. Med. Chem. 35, 1563-1572 (1992).4. Cheronis, J.C., et al. J. Med. Chem. 37, 348-355 (1994).5. Gera, L., et al. Immunopharmacology 33, 178-182 (1996).6. Howl, J., et al. FASEB J. 11, 582-590 (1997).7. Daffix, I., et al. J. Peptide Res. 52, 1-14 (1998).Mass found inMALDI-MS(m / z)Bioassay *RbApA 2R-715 none 1140.29 1140.48 8.42 ± 0.12NG2049 Adipoyl (n = 6) 2306.70 2307.86 8.43 ± 0.17NG2035 Suberyl (n = 8) 2334.76 2335.83 8.66 ± 0.19NG2050 Sebacoyl (n = 10) 2362.81 2362.97 7.69 ± 0.14NG2051 Dodecanedioyl (n = 12) 2390.86 2390.61 7.75 ± 0.12* Values are means ± S.E.M of 3-4 experiments. Inhibition of the contraction of the rabbitaorta (RbA) induced by the kinin B1R agonist desArg 9 -bradykinin (0.5 µM)461
Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Identification of a New Citrullinated Epitope on Filaggrin forthe Early Diagnosis of Rheumatoid ArthritisFruzsina Babos 1,2 , Eszter Szarka 1 , Ádám Bartos 2 , György Nagy 3 ,Gabriella Sármay 1,4 , Anna Magyar 2 , and Ferenc Hudecz 1,21 Department of Immunology, Eötvös Loránd University, Budapest, Hungary; 2 HAS-ELTEResearch Group of Peptide Chemistry, Budapest, Hungary; 3 Buda Hospital of HospitallerBrothers of St. John, Budapest, Hungary; 4 Immunology Research Group of the HungarianAcademy of Sciences at ELTE, Budapest, HungaryIntroductionAnti-citrullinated protein antibodies (ACPA) are sensitive and specific markers fordiagnosis and prognosis in Rheumatoid Arthritis (RA). Citrullination is a post-translationalmodification of arginine by deimination, induced by peptidylarginine deiminase (PAD). Itis a physiologically occurring phenomenon during apoptosis, inflammation or keratinization.Citrullination has been observed in different synovial proteins, including fibrinogen,vimentin [1] and collagen. Antibodiesspecific for cycliccitrullinated filaggrin [2] peptide(CCP1) were detected in RA seraand anti-CCP positivity is widelyused for diagnostic purposes.However, to determine theACPA-reacting epitopes onvimentin and new epitopes onfilaggrin would be useful in thediagnosis of anti-CCP3 seronegativepatients. Our aim was todevelop new tools for thedetection of ACPA and thus forthe early diagnosis of RA by theuse of clearly defined epitopes onfilaggrin and vimentin.OD ratioOD ratio15.012.510.015.012.510.07.55.02.50.07.55.02.50.0Filaggrin 306-324 XXXCCP3+ Healthy CCP3-CCP3+ vs Healthy P < 0.001CCP3+ vs CCP3- P < 0.001Healthy vs CCP3- P > 0.05Filaggrin 311-315 RXCCP3+ Healthy CCP3-CCP3+ vs Healthy P > 0.05CCP3+ vs CCP3- P < 0.05Healthy vs CCP3- P > 0.05OD ratio15.012.510.015.012.510.0Fig. 2. Multipin ELISA, measuring IgG.OD ratio7.55.02.50.07.55.02.50.0OD ratio6543210Filaggrin 306-324 XXXCCP3+ CCP3- HealthyCCP3+ vs CCP3-CCP3+ vs HealthyCCP3- vs HealthyP < 0.001P < 0.001P > 0.05Filaggrin 311-315 XRCCP3+ CCP3- HealthyFig. 1. Multipin ELISA, measuring IgG plus IgM.Filaggrin 311-315 XRCCP3+ Healthy CCP3-CCP3+ vs Healthy P < 0.05CCP3+ vs CCP3- P < 0.01Healthy vs CCP3- P > 0.05Filaggrin 311-315 XXCCP3+ Healthy CCP3-CCP3+ vs Healthy P < 0.01CCP3+ vs CCP3- P < 0.05Healthy vs CCP3- P > 0.05OD ratio6543210CCP3+ vs CCP3-CCP3+ vs HealthyCCP3- vs HealthyP < 0.001P < 0.001P > 0.05Results and DiscussionFirst, we used conventionalsolid-phase peptidesynthesis, carriedout on „MULTIPINNCP” non-cleavable kit(Mimetopes, Australia).Citrulline containingpeptides and the unmodifiedcounterpartscontaining argininewere synthesized on thepins in order to comparetheir respectivereactivities. We usedthese peptides-on-pinsin an indirect ELISAand ACPAs were determinedin the sera of RAand non-RA patientsusing anti-IgG plus IgMsecondary antibodies(Figure 1) and later IgG462
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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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