Proceedings book download - 5Z.com

More documents

Recommendations

Info

Table 2. Enzymatic Digestion of GnRH-III(Dau-spacer) conjugates by Cathepsin Ba, GnRH-III-Ttds(Ac-CALAL-Dau)b, GnRH-III-Ttds(Ac-CGGFL-Dau)MBHA resin. Daunorubicin was conjugated to the spacers via amide bond, while the spacersequences were attached to the GnRH-III peptide via thioether bond. The peptides and theconjugates were purified by semi-preparative RP-HPLC and characterized by analyticalRP-HPLC and mass spectrometry.Racemization was observed at the conjugation of spacer molecules containing Leu attheir C-terminus.The influence of the spacer sequences on the in vitro antitumor ativity of theconjugates was investigated on MCF-7 human breast and HT-29 human colon cancer cellsby MTT assay (Table 1).The drug release from the amide bond-linked GnRH-III(Dau-spacer) conjugates wasdetermined in the presence of Cathepsin B. In case of conjugates GnRH-III-Ttds-(Dau-AcCGFLG) and GnRH-III-Ttds-(Dau-AcCALAL), the smallest metabolites were Daucontaining tripeptides (H-LAL-Dau, H-FLG-Dau). The GnRH-III-Ttds-(Dau-AcCGFLG)conjugate degraded in the highest rate, followed by the GnRH-III-Ttds-(Dau-AcCALAL).No significant cleavage was observed in case of GnRH-III-Ttds-(Dau-AcCGGFL).The GnRH-III-Ttds-(Dau-AcCYRRL) conjugate has not been analyzed yet. Free Dau wasnot detected in the digestion mixtures.Degradation of the bioconjugates in lysosomal homogenates will be performed.Further experiments are needed to determine the correlation between the cytostatic effectand the metabolites.AcknowledgmentsThe authors thank to Hedvig Medzihradszky-Schweiger PhD, C.Sc. This study was supported bygrants from the Hungarian National Science Fund (OTKA NK77485, F 67884, K 81596), theUniversity of Konstanz (Zukunftskolleg, Project 879/08) and GVOP-3.2.1.-2004-04-0005/3.References1. Mező, G., et al. Collection Symposium Series 11, 72-76 (2009).2. Szabó, I., et al. Bioconjug. Chem. 20, 656-665 (2009).3. Calderon, M., et al. Bioorg. Med. Chem. Lett. 19, 3725-3728 (2009).4. Ajaj, K.A., et al. Cancer Chemother. Pharmacol. 64, 413-418 (2009).5. Bartos, Á., et al. Biopolymers 92, 110-115 (2009).517
Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010NAP-NS1: H-Cys-Ahx-ßAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Val-NH2NAP-NS2: H-Cys-Ahx-ßAla-c[Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2RRR[Tc(N)PNP] Metal Fragment Labeled Peptide for MC1Receptors Imaging: Preliminary StudiesBarbara Biondi 1 , Cristina Bolzati 2 , Davide Carta 3 , Nicola Salvarese 3 ,Fiorenzo Refosco 2 , Andrea Calderan 1 , and Paolo Ruzza 11 Institute of Biomolecular Chemistry of CNR, Padova Unit and Department of ChemicalSciences, University of Padova, Padova, 35131,Italy; 2 Institute of Inorganic Chemistry andSurfaces of CNR, Padova, 35020, Italy; 3 Department of Pharmaceutical Sciences,University of Padova, Padova, 35131, ItalyIntroductionMalignant melanoma is the most lethal form of skin cancer: melanoma metastases are veryaggressive and no curative treatment exists for it due to its resistance to chemotherapy andimmunotherapy regimens. Therefore, development of new melanoma-specific radiopharmaceuticalsfor early detection of primary melanoma tumours or internal radiotherapyis a subject of great interest. In this perspective, melanocortin type-1 receptors (MC1R)represent a promising target for the development of effective molecular probes fordiagnosis or therapy. MC1R are overexpressed on the surface of melanoma cells and ableto selectively recognise the peptide sequence His-D-Phe-Arg-Trp mimicking themelanocyte stimulating hormone ( MSH). The literature described several linear andcyclic radiolabeled MSH analogues. In particular, the introduction of a cyclic constraint ina lead peptide restricts the flexibility and may favour peptide–receptor interactions,receptor selectivity and enzymatic stability [1].In this work we synthesised linear and cyclic NAPamide analogues (Figure 1), inorder to improve their affinity toward MC1R and to be used as ligands in the formation of99m Tc complexes with the [ 99m Tc(N)(PNPn)] 2+ metal fragment [2]. We investigated the invitro stability in phosphate buffer solutions (PBS), in cysteine and glutathione solutions aswell as in rat liver (RLH) and kidney homogenates (RKH). Biodistribution studies wereperformed in female Sprague Dowley (S.D.) rats with [ 99m Tc(N)(NAP-NS1/2)(PNPn)] + inorder to evaluate their organ uptake and excretion pathways.Results and DiscussionPeptides were synthesised according to standard Fmoc/tBu method using HBTU/HOBt asPPRNNTcR'SH 2 NFig. 1. Peptide sequences and structure of complexes.CONHC-activation procedure. TheAhx- Ala sequence wasconjugated to the N-terminusof both peptides as a spacerbetween the radiolabeledmoiety and the binding regionto avoid interference betweenthe different portions of themolecule, while Cys residue isinvolved in complexformation. NAP-NS2 cyclizationwas performed on resin,using a Pd-mediateddeprotection of Alloc/Allylprotecting groups of Lys 4 andGlu 10 , respectively [3]. AfterHPLC purification, peptideswere obtained in good yieldswith a purity >98%.The [ 99m Tc(N)(peptide)(PNPn)] + complexes were prepared using two different methods.The first method is a two-step procedure: 1) the 99m Tc–nitrido precursors [ 99m Tc≡N] 2+ wasprepared by reaction of Na 99m TcO 4 (50.0 MBq-3.0 GBq) with succinic dihydrazide (SDH),SnCl 2 and ethanol in 30 minutes at room temperature; 2) the PNPn ligand and NAP-NS1/2were simultaneously added to [ 99m Tc≡N] 2+ , and the reaction mixture was heated at 80°C for518
Page 2 and 3:
Peptides 2010Tales of PeptidesProce
Page 4 and 5:
Peptides 2010Tales of PeptidesProce
Page 8 and 9:
IntroductionWe had the distinct hon
Page 10:
Scientific programIn planning the 3
Page 13 and 14:
31 st EUROPEAN PEPTIDE SYMPOSIUMSep
Page 19 and 20:
published by John Wiley & Sons as a
Page 21 and 22:
The Josef Rudinger AwardThis award
Page 23 and 24:
Young Investigators' SymposiumThe y
Page 25 and 26:
xxiv
Page 27 and 28:
Design of Peptidyl-Inhibitors for G
Page 29 and 30:
Synthetic Antifreeze Glycopeptide A
Page 31 and 32:
Synthesis and Oxidative Folding of
Page 33 and 34:
Convergent Syntheses of Huprp106-12
Page 35 and 36:
Bactericidal Activity of Small Beta
Page 37 and 38:
Bradykinin Analogues Acylated on Th
Page 39 and 40:
Antimicrobial Activity of Small 3-(
Page 41 and 42:
Interaction of Curcumin with A-Synu
Page 43 and 44:
Fluorescent and Luminescent Fusion
Page 45 and 46:
Cellular Expression of the Human An
Page 47:
2D IR Spectroscopy of Oligopeptides
Page 50 and 51:
large, non-redundant subset of prot
Page 52 and 53:
The aberrantly glucosylated peptide
Page 54 and 55:
Table 1. Proline cis/trans ratios o
Page 56 and 57:
Table 1. Yields, UV-vis absorption
Page 58 and 59:
Table 1. Purity of the targeted tri
Page 60 and 61:
processes are blocked. Interestingl
Page 62 and 63:
(tb4 n ,1 m )MTII(tb1 n ,4 m )MTIIF
Page 64 and 65:
Fig. 2. a) Part of the 400 MHz HR-M
Page 66 and 67:
Once printed, the amino acid partic
Page 68 and 69:
A) PSA, few seconds73B) PSA, 45 min
Page 70 and 71:
short β strands. In contrast, nume
Page 72 and 73:
neg. control Cs9-Rhd MM-218Fig. 2.
Page 74 and 75:
Table 1. The general structure of t
Page 76 and 77:
% ID in the liver 1 h p.i.100908070
Page 78 and 79:
Peptidyl phosphoranes were first re
Page 80 and 81:
obtained from the same sardines and
Page 82 and 83:
MccJ25 variants were produced by si
Page 84 and 85:
Fig. 2. Proposed signaling mechanis
Page 86 and 87:
Table 1. mCD4-HS12 antiviral activi
Page 89 and 90:
Proceedings of the 31 st European P
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
RT: 0,00 - 5,9936000034000032000030
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 267 and 268:
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
Page 357 and 358:
Page 359 and 360:
Page 361 and 362:
Page 363 and 364:
Page 365 and 366:
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
Page 379 and 380:
Page 381 and 382:
Page 383 and 384:
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
Page 405 and 406:
Page 407 and 408:
Page 409 and 410:
Page 411 and 412:
Page 413 and 414:
Page 415 and 416:
Page 417 and 418:
Page 419 and 420:
Page 421 and 422:
Page 423 and 424:
Page 425 and 426:
Page 427 and 428:
Page 429 and 430:
Page 431 and 432:
Page 433 and 434:
Page 435 and 436:
Page 437 and 438:
Page 439 and 440:
Page 441 and 442:
Page 443 and 444:
Page 445 and 446:
Page 447 and 448:
Page 449 and 450:
Page 451 and 452:
Page 453 and 454:
Page 455 and 456:
Page 457 and 458:
Page 459 and 460:
Page 461 and 462:
Page 463 and 464:
Page 465 and 466:
Page 467 and 468:
Page 469 and 470:
Page 471 and 472:
Page 473 and 474:
Page 475 and 476:
Page 477 and 478:
Page 479 and 480:
Page 481 and 482:
Page 483 and 484:
Page 485 and 486:
Page 487 and 488:
Page 489 and 490:
Page 491 and 492:
Page 493 and 494:
Page 495 and 496:
Page 497 and 498:
Page 499 and 500:
Page 501 and 502:
Page 503 and 504:
Page 505 and 506:
Page 507 and 508:
Page 509 and 510:
Page 511 and 512:
Page 513 and 514: Proceedings of the 31 st European P
Page 563: Proceedings of the 31 st European P
Page 615 and 616:
Page 617 and 618:
Page 619 and 620:
Page 621 and 622:
Page 623 and 624:
Page 625 and 626:
Page 627 and 628:
Page 629 and 630:
Page 631 and 632:
Page 633 and 634:
Page 635 and 636:
Page 637 and 638:
Page 639 and 640:
Page 641 and 642:
Page 643 and 644:
Page 645 and 646:
Page 647 and 648:
Page 649 and 650:
Page 651 and 652:
Page 653 and 654:
Page 655 and 656:
Page 657 and 658:
Page 659 and 660:
Page 661 and 662:
Page 663 and 664:
Page 665 and 666:
Page 667 and 668:
Page 669 and 670:
Page 671 and 672:
Page 673 and 674:
Page 675 and 676:
Page 677 and 678:
Page 679 and 680:
Subject index(S)-2-(1-adamantyl)gly
Page 681 and 682:
chip 18chiral triazine condensing r
Page 683 and 684:
heat stress 348helical conformation
Page 685 and 686:
O-acyl isopeptide method 112obesity
Page 687 and 688:
SH2-ligands 210short collagen-relat
Page 689 and 690:
Author indexAboye, Teshome Leta 142
Page 691 and 692:
Chi, Hongfang 480Chiche, Laurent 6C
Page 693 and 694:
Geronikaki, Athina 444Gessmann, Ren
Page 695 and 696:
Kostova, Kalina 528Kotzia, Georgia
Page 697 and 698:
Nagata, Koji 162Nagayev, Igor Yu. 5
Page 699 and 700:
Salvarese, Nicola 518Sammet, Benedi
Page 701 and 702:
Vauquelin, Georges 138Veiga, Ana Sa
show all

Proceedings book download - 5Z.com

Create successful ePaper yourself

Delete template?

Save as template?