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Fig. 2. Synthesized peptides and (A) Inhibition of [ 125 I]Epibatidine binding toimmunoimmobilised striatal α6β2* receptors induced by native PIA, ∆R-PIA, ∆RD-PIAand ∆RDP-PIA peptides; (B)Affinity of [E11R]MII and [E11R]RDP-MII peptides forα6β2*; (C) affinity of [E11R]MII and [E11R]RDP-MII peptides for the native α3β2*.affected at the α3β2* subtype (Figure 2C). Unlike PIA, MII also binds the α3β2 subtypewith relatively high affinity, and molecular modeling investigations showed that theglutamic acid (E) residue in position 11 plays a primary role in piloting molecularrecognition. We therefore designed and synthesised new analogues of MII in which E11was replaced by R [i.e., (E11R)MII and (E11R)RDP-MII)], and found that they displayedthe same potency and affinity for native rat α6β2* as MII and RDP-MII (Figure 2B), butlower affinity and potency for the native and heterologously expressed α3β2* subtype(Figure 2C). Hence, the novel (E11R)MII and (E11R)RDP-MII peptides are potent andselective α6β2* antagonists.In conclusion, we designed and synthesised new analogues of MII in which E11 wasreplaced by R (i.e., [E11R]MII and [E11R]RDP-MII), and found that they displayed a) thesame potency and affinity for native rat α6β2* nAChRs as MII and RDP-MII, and b) loweraffinity and potency for the native and heterologously expressed α3β2* subtype. Hence, thenovel [E11R]MII and [E11R]RDP-MII peptides are potent and selective α6β2* vs. α3β2*antagonists.AcknowledgmentsThis study was financially supported by the Italian research grants: FIRB # RBNE03FH5Y002 andPRIN # 20072BTSR2References1. Gotti, C., Zoli, M., Clementi, F. Trends Pharmacol. Sci. 27, 482-491 (2006).2. Gotti, C., et al. Biochem. Pharmacol. 78, 703-711 (2009).3. Olivera, B.C., et al. Channels (Austin) 2, 143-152 (2008).575
Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Molecular Modeling of Novel GnRH Analogues Using NMRSpectroscopy and Relation with Their Anti-Cancer ActivitiesF. Tahoori 1 , M. Erfani Moghaddam 2 , A. Arabanian 1 , and S. Balalaie 1*1 Peptide Chemistry Research Center, K.N. Toosi University of Technology, Tehran,P.O. Box 15875-4416, Iran; 2 Department of Biological Science, Tarbiat ModaresUniversity, Tehran, P.O. Box 14115-111, Iran;* balalaie@kntu.ac.irIntroductionGonadotropin Releasing Hormone (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 ,GnRH) plays a significant role in the controlling of gonadotropins and steroidhormones [1]. Considerable effort has been dedicated to the synthesis of peptide mimeticstructures to overcome the unfavorable properties and also therapeutic deficiencies ofpeptides [2].Among them is insertion of some chemical groups in the peptide sequences to increasetheir activity. In the present work, new GnRH analogues were designed, synthesized andanalyzed for its anti-cancer activity in comparison with triptorelin acetate. The newanalogue structure is similar to triptorelin acetate with two extra chemical groups insertedbetween Leu7 and Arg8 in order to increase peptide hydrophobic properties without anychange in peptide active sites (I).Results and DiscussionIn a continuation of our research work for the synthesis of pharmaceutical peptides, and inorder to study the effect of modification in triptorelin acetate structure, the new triptorelinanalogue was designed, and synthesized via an efficient Ugi-4MCR (Figure 1) [3].Reaction of heptapeptide which contained free carboxylic acid and tripeptide with freeamino group, 4-pyridine carbaldehyde and cyclohexyl isocyanide leads to the desiredcompound (I). The heptapeptide was synthesized using Fmoc SPPS standard strategy ingood yield. The anti-cancer activity of analogue (I) was studied. It showed better anticanceractivity compared to triptorelin acetate. In the extra pituitary compartment GnRHand its receptor act as part of the autocrine regulatory system of cell proliferation, resultingin its anticancer activity. The inhibitory efficiency of this new analogue is proved to behigher than the original triptorelin [4].CHONp-Glu-His(Trt)-Trp(Boc)-Ser(tBu)-Tyr(tBu)-D-Trp-Leu-COOH + H 2 N-Arg(Pbf)-Pro-Gly-CONH 2p-Glu-His-Trp-Ser-Tyr-D-Trp-LeuFig. 1. Synthesis of novel GnRH analogue using Ugi-4MCR.C N Cy-hexyl1) MeOH2) Reagent KNHN Cy-hexylNOArg-Pro-Gly-CONH 2Herein, the sample was dissolved in DMSO-d6 and TOCSY and NOESY 2D spectra wererecorded using a Bruker Avance DRX-500 spectrometer. The data acquisition were(I)O576
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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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Page 571 and 572: 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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