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Table 1. Room temperature- vs MW-assisted synthetic approachSPPS strategy Purity of crude peptide (%)% Yield of pure >95%peptide (mg)Room temperature 35 4.4 (18 mg)MW-assisted 77 6.3 (27 mg)In conclusion, microwave technology has improved SPPS of particularly difficultsequences as compared with the conventional room temperature method. This improvementis attributed to prevention of peptide backbone aggregation and acceleration of deprotectionand coupling steps.In general, MW-assisted SPPS is proposed as a reliable strategy to overcome somelimitations encountered in conventional SPPS. In our case, although the application ofmicrowaves in SPPS led only to moderate improvement in final yield it allowed us toobtain a crude PTHrP(1-34)NH 2 of higher quality and enabled the development of a fastmicro-cleavages as an alternative method for monitoring SPPS.Therefore, based on our experience, the advantages of MW-assisted SPPS vsRT-SPPS can be summarized as follow: 1) shortening reaction time, 2) shorteningmicro-cleavage time, 3) crude peptides of higher quality facilitating the subsequentpurification steps.AcknowledgmentsEnte Cassa Risparmio di Firenze and ANR Chaire d’Excellence 2009-2013 PepKit (France) aregratefully acknowledged.References1. Stewart, A.F. N. Engl. J. Med. 352, 373-379 (2005).2. Wysolmerski, J.J., Stewart, A.F. Annu. Rev. Physiol. 60, 431-460 (1998).3. Horiuchi, N., et al. Science 238, 1566-1568 (1987).4. Sabatino, G., Papini, A.M. Curr. Opin. Drug Discov. Devel. 11, 762-770 (2008).189
Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Microwave-Assisted Total Synthesis of MacrocyclicCystine Knot MiniproteinsS. Park, S. Gunasekera, T. Aboye Teshome, and U. GöranssonDiv. of Pharmacognosy, Dept. of Medicinal Chemistry, Uppsala University,BMC Box 574, SE-751 23, Uppsala, SwedenIntroductionCyclotides are mini-proteins of approximately 30 amino acids residues that have a uniquestructure consisting of a head-to-tail cyclic backbone with a knotted arrangement of threedisulfide bonds [1] (Figure 1). This unique structure provides exceptional stability tochemical, enzymatic and thermal treatments [2] and has been implicated as an ideal drugscaffold for the development into agricultural and biotechnological agents [3]. Wedeveloped the first method for microwave assisted Fmoc-SPPS of cyclotides [4]. Weovercame the difficulties that previous studies [5-7] encountered for synthesis of cyclicpeptides which involves numerous and time consuming reaction steps.Results and DiscussionThe protocol adopts a strategy that combines the optimized microwave assisted chemicalreactions for Fmoc-SPPS of peptide backbone synthesis, thioesterification of theC-terminal carboxylic acid of the peptide and a one pot reaction that promotes cyclisationthrough native chemical ligation and oxidative folding (Figure 1). The application of thisprotocol was exemplified for the synthesis of three prototypic cyclotides; kalata B1,MCoTI-II and cycloviolacin O2.By utilization of current protocol, the results are as follows. For peptide chainelongation, microwave assisted coupling reaction showed the yield higher than 99.3%.With microwave application, the cleavage time was effectively shortened from 3 hours atroom temperature into 45 minutes. Thioester was efficiently introduced at C-terminalprotected peptide; LC-MS analysis confirmed full conversion into thioester withPyBOP/p-acetamidothiophenol/DIPEA (5/5/10 equiv) in DMF under microwave radiation.190Fig. 1. Synthetic strategy forsynthesis of cyclotides. (a) Assemblyof the protected peptide backbone byMW assisted Fmoc SPPS (couplingreaction for non-Cys: 5 min, 35W,75 o C for Cys: 7min, 30W, 55 o C); (b)AcOH/TFE/DCM (1/1/8) undermicrowave radiation (45 min, 10W,40 o C); (c) (1) PyBOP/p-acetamidothiophenol/DIPEA (5/5/10 equiv) inDMF under microwave radiation(5 min, 35W, 75 o C), (2) TFA/TIPS/water (95/2.5/2.5), rt, 2 hr; (d) 1:1(v/v) mixture of 0.25 M Tris buffer(pH 8.0) and isopropanol, containingreduced and oxidised glutathione (8respective 2 mM), rt, 24 hr.
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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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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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