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84 (chronic myeloid leukemia), SKW-3 (human T-cell leukemia), HD-MY-Z (Hodgkinlymphoma), DOHH-2 (non-Hodgkin lymphoma), 5637 and EJ (human urinary bladdercarcinoma). The effects were assessed by the MTT-dye reduction assay in a wideconcentration range (1-500 µМ) with varying the exposure periods (24, 48, 72 or 96 h). Thereference angiostatic drug thalidomide (THAL) and the sesquiterpene lactonehydroxyartemisinine (ART-OH) (with established anticancer and antiangiogenic effects)were used as positive controls throughout the study (Table 1). The tested arginineanalogues demonstrated only marginal effects and failed to cause 50% inhibition of cellularviability even after 3 days exposure.Table 1. Antiproliferative effects of the tested compounds against a spectrum of humantumor cell lines, as assessed by the MTT-dye reduction assayIC 50 values (µM)Cell linesNNC NNA NsArg CAV THALART-OH72 h 96 h 72 h 96 h 72 h 96 h 72 h 96 h 72 h 72 hK-562 >500 >500 >500 >500 >500 >500 >500 >500 85 >100HL-60 >500 >500 >500 >500 >500 >500 >500 >500 39 >100HD-MY-Z >500 >500 >500 >500 >500 >500 >500 >500 70 >100DOHH-2 >500 >500 >500 >500 >500 >500 >500 >500 47 >1005637 >500 >500 >500 >500 >500 >500 >500 >500 29 >100EJ >500 >500 >500 >500 >500 >500 >500 >500 90 >100“Cell Death Detection” ELISAIn order to elucidate the mechanisms underlying the angiostatic effects of testedcompounds we analyzed their propensity to induce apoptosis in VEGF-stimulated HUVEC(Figure 2). To meet this objective we assessed the oligonucleosomal fragmentation of DNAin treated vs non-treated cells after 24 h exposure at concentrations higher than TGI.Compounds NNC, NNA and NCMe did not trigger apoptosis, which is in line with theMTT-data showing lack of cytotoxic effects. Some increase of the level of histoneassociated DNA-fragments was evoked only with CAV, which indicates that the inductionof apoptosis is at least partly implicated in the observed cytotoxic effects against VEGFstimulatedHUVEC.In conclusion we could say that new polyarginines were synthesized. The abnormalproliferative activity of vascular endothelium is a crucial event in tumor-inducedangiogenesis. The preliminary screening for antiproliferative and cytotoxic effects of testedbuilding amino acids against a spectrum of six human cell lines revealed that theestablished inhibitory activity, together with the low cytotoxicity, give us reason toconsider these compounds as prospective leads for development of antiangiogenic agents.AcknowledgmentsWe are grateful to the the Bulgarian Ministry of Education and Science and NFSR of Bulgaria(Contract MY-FS-13-07).References1. Tung, C., Weissleder, R. Adv. Drug Delivery Rev. 55, 281-294 (2003).2. Pajpanova, T., Stoev, S., Golovinsky, E., Krauss, G.-J., Miersch, J. Amino Acids 12, 191-204 (1997).3. Videnov, G., Aleksiev, B., Stoev, M., Pajpanova, T., Jung, G. Liebigs Ann. Chem. 941-945 (1993).4. Dzimbova, T., Pajpanova, T., Tabakova, S., Golovinsky, E. In: 5th Hellenic Forum on BioactivePeptides, TYPORAMA, Greece, Cordopatis P. (Ed.) 223-227 (2007).515
Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Synthesis and Biological Evaluation of Daunorubicin-GnRH-IIIProdrugRózsa Hegedüs 1 , Erika Orbán 1 , Ildikó Szabó 1 , Marilena Manea 2,3 , andGábor Mező 11 Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L.University, Budapest, Hungary, 2 Laboratory of Analytical Chemistry and BiopolymerStructure Analysis, Department of Chemistry, University of Konstanz, Konstanz, Germany;3 Zukunftskolleg, University of Konstanz, Konstanz, GermanyIntroductionTumor targeting with the decapeptide gonadotropin-releasing hormone (GnRH) or itsanalogs is based on the discovery that GnRH receptors are highly expressed in many tumorcells (e.g., prostate, ovarian, breast, endometrial), compared with their expression in normaltissues. Therefore, these peptides could be used as carriers/targeting moieties to whichtherapeutic agents are attached leading to the formation of conjugates with increasedselectivity and lower toxic side effects. The lamprey GnRH-III (
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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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