Innovation and Perspectives in

OLID PHASESYNTHESIS& COMBINATORIAL LIBRARIES

Peptides, Proteins and Nucleic AcidsSmall Molecule Organic Chemical Diversity

1996Editor: Roger Epton

Collected PapersFourth International Symposium12th -16th September, 1995Edinburgh, Scotland, UK

Mayflower Scientific Limited, Birmingham, 1996

TABLE OF CONTENTS

Preface v

Acknowledgements vi

SYNTHESIS / STRATEGY OF SYNTHESIS

1. METHODOLOGY FOR CHEMICAL SYNTHESIS OF PROTEINS 1R. Ramage, G.W. Biggin, A.R. Brown, A. Comer, A. Davison, L. Draffan,Lu Jiang, G. Morton, N. Robertson, K.T. Shaw, G. Tennant, K. Urquhartand J. Wilken

2. SOLID PHASE SYNTHESIS OF OLIGORIBONUCLEOTIDES CONTAININGSITE-SPECIFIC MODIFICATIONS 11

Sabine Schmidt, Richard L. Grenfell, Jan Fogg, Terry V. Smith, Jane A. Grasby,Karin Mersmann and Michael J. Gait.

3. THE SYNTHESIS, AND SEPARATION OF PEPTIDES, DNA AND HYBRIDMOLECULES 19

Ronald M. Cook and Derek Hudson

Advances in Solid Phase Peptide/Protein Synthesis (I)

4. CHEMICAL SYNTHESIS OF PROTEINS: A PRACTICAL SOLID-PHASESEGMENT ASSEMBLY APPROACH 27

Tony Johnson, Leonard C. Packman and Martin Quibell

5. AN EFFICIENT AND RELIABLE SOLID PHASE SEGMENT ASSEMBLYAPPROACH FOR SMALL PROTEIN SYNTHESIS THROUGH THE USE OFBACKBONE AMIDE-PROTECTED PEPTIDE SEGMENTS 37

Martin Quibell, Leonard C. Packman and Tony Johnson

6. ADVANCES IN THE USE OF ONIUM-BASED COUPLING REAGENTS:APPLICATION FOR SOLID-PHASE PEPTIDE SYNTHESIS ANDCOMBINATORIAL LIBRARIES 41

Steven A. Kates, Salvatore A. Triolo, G. William Griffin, Lee W. Herman,George Tarr, Nura A. Sole, Elke Diekmann, Ayman El-Faham,Dumitru Ionescu, Fernando Albericio and Louis A. Carpino

Advances in Solid Phase Oligonucleotide DNA, RNA, PNA etc. Synthesis (I)

i. SYNTHESIS OF PNA ON A PEPTIDE SYNTHESIZER: SOLID PHASE-PNAAFFINITY PROBES FOR SEQUENCE SPECIFIC ISOLATION FROM TOTALDNA !":.:.. 51

Ken Otteson, Dave Knorr and Alex Andrus

8. SYNTHESIS AND APPLICATIONS OF SPATIALLY ADDRESSABLEOLIGONUCLEOTIDE ARRAYS 57

Stephen C. Case-Green, Kalim U. Mir, Natalie Milner and Edwin M. Southern

9. SYNTHESIS OF POLY AMIDE NUCLEIC ACIDS USING A NEWPROTECTION SCHEME WHICH IS FULLY COMPATIBLE WITHOLIGONUCLEOTIDE SYNTHESIS 61

G. Breipohl, D.W. Will, D. Langer, J. Knolle and E. Uhlmann

10. SOLID-PHASE SYNTHESIS OF PNA-DNA CHIMERIC OLIGOMERS 65D.W. Will, G. Breipohl, D. Langner and E. Uhlmann

11. PHYSICOCHEMICAL PROPERTIES OF 1,5-ANHYDRO-HEXITOL

NUCLEIC ACIDS 69

Arthur Van Aerschot, Chris Hendrix, Use Verheggen and Piet Herdewijn.

SYNTHESIS / AUTOMATED SYNTHESIS / APPLICATIONS

Automated Solid Phase Synthesis

12. AUTOMATED PEPTIDE SYNTHESIS UTILIZING URETHANE-PROTECTEDN-CARBOXYANHYDRIDES (UNCA'S) 73

Murray Goodman, Susan H. H. Wang, Jaimie K. Rueter, Joseph P. Taulane andJacqueline McCandless

13. SYNTHESIS OPTIMISATION USING ON-LINE MONITORING IN A NEWCONTINUOUS FLOW SYNTHESIZER 87

H. Gausepohl, C. Behn, R. Schopfer and R. W. Frank

14. MARS - MULTIPLE AUTOMATIC ROBOT SYNTHESIZER FEATURING ANOVEL TIMING PROCEDURE AND RANDOM ACCESS TO REAGENTS ANDREACTION VESSELS 93

Viktor Krchnak and Michal Lebl

15. MINIATURIZATION IN CHEMISTRY: CHEMICAL POSSIBILITIES ANDPHYSICOCHEMICAL PROPERTIES OF POLYMERIC MICROREACTORS 97

W. Rapp, G. Nicholson, M. Maier, G. Schlotterbeck, M. Purschand K. Albert

Small Molecule Organic Chemical Libraries (I & II)

16. SYNTHESIS OF BINARY ENCODED SMALL MOLECULE LIBRARIES ANDTHEIR APPLICATION TO DRUG DISCOVERY AND OPTIMIZATION 101

John C. Chabala, John J. Baldwin, Jonathan J. Burbaum, Daniel Chelsky,Lawrence W.Dillard, Ian Henderson, Ge Li, Michael H. J. Ohlmeyer,Troy L. Randle, John C. Reader, Laura Rokosz and Nolan H. Sigal

17. THE USE OF POLYMER-ASSISTED ORGANIC SYNTHESIS FOR THEPRODUCTION OF SMALL ORGANIC MOLECULES 107

Irving Sucholeiki

Vll l

18. SOLID PHASE POLYAMINE LINKERS - SYNTHESIS AND COMBINATORIALUTILITY I l l

Ian Marsh, Helen Smith, Catherine Leblanc and Mark Bradley

19. SYNTHESIS OF QUINOLINE ANTIBIOTICS BY DIVERSOMER™TECHNOLOGY 115

Alasdair A. MacDonald, Sheila Hobbs De Witt, Eleonora Hoganand Robert Ramage

Advances in Solid Phase Peptide / Protein Synthesis (II)

20. USE OF THE ALLYLIC HYCRON ANCHOR IN SOLID PHASE PEPTIDESYNTHESIS 117

Markus Gewehr, Horst Kunz, Arnulf Lauterbach, Birgit Lohr and Oliver Seitz

21. N-PROTECTED AMINOACYLOXOCROTONATES - VERSATILE NEWTOOLS IN PEPTIDE SYNTHESIS COMBINING BOTH SOLUTIONAND SOLID PHASE HYCRAM® ADVANTAGES 121

Christian Birr, Giinther Braum and Axel Lifferth

22. PREPARATION OF Ca-METHYL AMINO-ACIDS AND THEIR USE INSOLID PHASE SYNTHESIS 125

M. Ayoub, A. Brunissen, G. Chassaing, S. Lavielle and A. Loffet

23. AMINO ACID FLUORIDES IN PEPTIDE SYNTHESIS - EFFICIENT ACYLATIONOF HYDROXYL FUNCTIONS AND EXTENSION OF THE METHOD TO VERYBULKY AMINO ACID RESIDUES 131

Holger Wenschuh, Michael Beyermann, Dorthe Granitza, Hanka Haber,George A. Truran, Michael Bienert and Louis A. Carpino

Advances in Nucleic Acid Synthesis (II)

24. OPTIMIZED AUTOMATED SOLID PHASE SYNTHESIS OFOLIGONUCLEOTIDES AND DERIVATIVES 135

G. Alvarado Urbina, W. Voelter, A. Weiler, H. Echner, S. Stoeva,J.P.Schernthaner, W.Reinig, G. Grubler and W. Gross

25. SOLID-PHASE SYNTHESIS OF OLIGONUCLEOTIDE AND PEPTIDEDITHIOPHOSPHATES 141

Peter H. Seeberger, Jennifer L. Jordan, and Marvin H. Caruthers

26. AN EFFICIENT DEPROTECTION STRATEGY FOR AUTOMATEDOLIGONUCLEOTIDE SYNTHESIS USING A NOVEL SILYLLINKED SOLID SUPPORT 147

Anne Routledge, Mark P. Wallis, Kenneth C. Ross and William Fraser

Peptide Libraries / Library Applications (I)

27. COMBINATORIAL CHEMISTRY: PAST AND PRESENT DEVELOPMENTS 151Arpad Furka, Eugen Campian, Mark Peterson, Hossain Saneiiand Joanne Chou

28. THE ZINC FINGER MOTIF AS A CONFORMATION-INDUCING TEMPLATEFOR SELECTION-DRIVEN DESIGN OF PEPTIDOMIMETICS 159

Elisabetta Bianchi, Gaetano Barbato, Andrew Wallace, Riccardo Cortese,Franco Felici, Renzo Bazzo and Antonello Pessi

SYNTHESIS / BIOLOGICAL & BIOMEDICAL APPLICATIONS

Peptide Vaccine Assemblies / Development

29. POLYMER-SUPPORTED COMBINATIONS OF PEPTIDE EPITOPES FROMHIV-1 gP120/gp41 OR FeLV env. - SUGGESTIONS FOR SYNTHETICVACCINE CONSTRUCTS 163

Christian Birr, Klaus Friebel, Gerhard Becker, Sigrid Nick, Gerald Voss,Hubert Bayer and Gerhard Hunsmann

30. NOVEL PEPTIDE TREATMENTS OF IgE ALLERGIES 173Denis R. Stanworth

Advances in Solid Phase Peptide / Protein Synthesis (III)

31. RECENT PROGRESS ON THE FORMATION OF SULFUR-SULFURBRIDGES IN PEPTIDES 181

George Barany and Lin Chen

32. BACKBONE AMIDE (BAL) ANCHRING IN SOLID PHASE PEPTIDESYNTHESIS ...,.-. 187

Knud J. Jensen, Michael F. Songster, Jordi Alsina, Josef Vagner,Fernando Albericio and George Barany

33. NOVEL HIGHLY CROSS-LINKED SUPPORTS FOR SOLID PHASEAPPLICATIONS 191

Maria Kempe and George Barany

34. THE PURIFICATION OF PROTECTED PEPTIDE SEGMENTS 195Paul Lloyd-Williams, Fernando Albericio, Margarida Gairand Ernest Giralt

Peptide Libraries / Library Applications (II)

35. POSITIONAL SCANNING COMBINATORIAL LIBRARIES BUILT AROUNDMONO-AND BICYCLIC PEPTIDE TEMPLATES 201

Jutta Eichler, Adam W. Lucka and Richard A. Houghten

x

36. SIMULTANEOUS MULTIPLE SYNTHESIS OF BACKBONE-CYCLIC PEPTIDELIBRARIES 205

Chaim Gilon, Gal Bitan, Irina Zeltser and Dan Muller

37. POTENTIAL APPLICATIONS OF CYCLIC PEPTIDE LIBRARIES 209Philip E. Thompson, Vittoria Cavallaro and Milton T.W. Hearn

38. COMBINATORIAL SYNTHESIS OF PEPTIDE-INTERCALATOR-PEPTIDECONJUGATES 213

Glenn Tong and John Nielsen

Biologically / Biomedically-significant Peptides / Proteins (I)

39. THE ROLE OF PRIMARY AND SECONDARY STRUCTURE IN ANTIBODYRECOGNITION OF A PROTEIN CORE EPITOPE FROM THE TANDEM REPEATUNIT OF MUC2 GLYCOPROTEIN: THE USE OF D-AMINO ACIDSUBSTITUTED FLANKS 217

Katalin Uray, Judit Kajtar, Michael R. Price, Ferenc Hudecz

40. CHEMICAL SYNTHESIS AND BIOLOGICAL ACTIVITY OF RELAXINPEPTIDES 223

John D Wade, Daniela Salvatore, Feng Lin and Geoffrey W Tregear

41. SOLID-PHASE SYNTHESIS OF DIFFERENT GALANINS, THEIR SEGMENTSAND ANALOGS 227

Lajos Balaspiri, Tamas Janaky, Csaba Somlai, Marianna Mak, Jr.Laszlo Otvos,Gabor Blazso, Tamas Takacs and Peter Kasa

Methodology - Application to Large Scale Solid Phase Synthesis

42. SUPPRESSING RACEMIZATION IN THE REGENERATION PROCEDUREOF FMOC-AMINOACID DERIVATIVES RECOVERED FROMPEPTIDE SYNTHESIS 233

Michael Kiffe, Yoshio Yokomizo and Kiyoshi Nokihara

43. HIGH-LOADED SUPPORTS AND THE NPE/NPEOC-STRATEGY:AN EFFICIENT COMBINATION FOR LARGE SCALE SYNTHESISOF OLIGONUCLEOTIDES 239

Jan Weiler and Wolfgang Pfleiderer

44. PHASE CHANGE DURING PEPTIDE SYNTHESIS 243Panagiotis Athanassopoulos, Kleomenis Barlos, Olga Hatzi,Dimitris Gatos and Chryssoula Tzavara

Biologically / Biomedically-significant Peptides / Proteins (II)

45. THE P-THYMOSIN STORY 247Wolfgang Voelter, Khalid Mohammed Khan, Hartmut Echner,Gerald Griibler, Hans Zimmermenn, Rania Tsitsiloniand Stanka Stoeva

xi

46. NMR STUDIES OF THE 11-RESIDUE CYTOPLASMIC PEPTIDE THATBRIDGES TWO TRANSMEMBRANE HELICES OF THE HIGHAFFINITY IgE RECEPTOR 253

Mire Zloh, Rodplfo R. Biekofsky, Ettore Benedetti, Malcom Danton,Istvan Toth and William A. Gibbons

47. CHEMICAL SYNTHESIS, STRUCTURE AND BIOCHEMICAL FUNCTION OFMYCOBACTERIUM TUBERCULOSIS CHAPERONIN 10 259

G. Fossati, P. Lucietto, H.L. Ball, P. Giuliani, E. Chan, A. Zaliani, G.Legname, S. Harding, H. Colfen, A.R.M. Coates and P. Mascagni

Solid Phase Glycopeptides (I & II) - Opiod Peptides

48. RECENT TECHNIQUES IN GLYCOPEPTIDE SYNTHESIS AND BIOLOGY:THE GLYCOPEPTIDE TEMPLATES , 263

Morten Meldal, Henrik Franzyk, Ernst Meinjohanns,Antonio Vargas-Berenguel, Klaus Frische, Mette Knak Christensen,Ida Christiansen Brams, Knud J0rgen Jensen and Klaus Bock

49. EXPLORING THE DIVERSITY OF MONO- AND OLIGOSACCHARIDESTRUCTURES IN THE SYNTHESIS, CONFORMATIONAL ANALYSISAND BIOMEDICAL APPLICATION OF GLYCOPEPTIDES 269

Laszlo Otvos, Jr., Laszlo Urge, Gyorgyi I. Szendrei, Barbara Cappelletto,Istvan Varga, Katherine Vogele Prammer and Hildegund C.J. Ertl

50. SYNTHESIS AND PHARMACOLOGY OF O-LINKED GLYCOPEPTIDEENKEPHALIN ANALOGUES: A NEW CLASS OF OPIOID ANALGESICS 277

Robin Polt, Lajos Szabo, V. J. Hruby, T. P. Davis, Frank Porrecaand H. I. Yamamura

51. SOLID PHASE SYNTHESIS OF A DIRECTED SMALL ORGANIC LIBRARY:DISCOVERY OF A NEW CLASS OF DELTA OPIOD DRUG LEAD 281

Marguerite M. Letulle, Nathan Collins, Peg Davis, Richard Knapp,Kathy Lee, Hank Yamamura, Frank Porreca and Victor J. Hruby

Biologically / Biomedically-significant Peptides / Proteins (III)

52. DESIGN OF SELECTIVE, FLUOROGENIC SUBSTRATES FOR MEMBERS OFTHE MATRIX METALLOPROTEINASE FAMILY 285

Gregg B. Fields and Michael W. Pennington

53. DETERMINING Sn' SPECIFICITIES OF SERINE PROTEINASES USINGCOMBINATORIAL PEPTIDE LIBRARIES, AND EVIDENCE THATENZYMES CAN PENETRATE TENTAGEL RESIN BEADS 291

Gordon Lowe and Rachel Quarrell

54. A NATURAL a/p SCAFFOLD FOR THE DESIGN AND SYNTHESIS OF NOVELPROTEINS 295

Claudio Vita, Eugenia Drakopoulou, Carole Leon, Sophie Zinn-Justin,Marc Guenneugues and Andre Menez

xii

POSTER PAPERS

55. SYNTHESIS OF HUMAN GUANYLIN: TEMPERATURE-DEPENDENT HPLC,CZE AND NMR STUDIES VERIFY STEREOISOMERISM OF ADISULFIDE-CONTAINING PEPTIDE 299

Knut Adermann, Susanne Neitz, Ute C. Marx, Paul Roschand Wolf-Georg Forssmann

56. DARAS™ (DNA AND RNA ANALYSIS SYSTEM) 303Ayo A Akinsanya, Simon J Barker, Allan Brown, Ian R Hudson,John D Oultram and Stephen J Minter

57. SYNTHESIS OF CLASS I MAJOR HISTOCOMP AT ABILITY COMPLEXBINDING PHOSPHOPEPTIDES 307

G. Arsequell, J. Haurum, T. Elliot and G. Valencia

58. DESIGN OF INHIBITORS TO THE ATP BINDING SITE OF DNATOPOISOMERASES II 309

Liliane Assairi

59. A NEW VERSATILE CARRIER DERIVED FROM MAP FOR IMMUNOLOGICALSTUDIES 313

Franchise Baleux, Philippe Dubois and Helene Jouin

60. SOLID PHASE SYNTHESIS OF A AND B CHAINS OF HUMAN INSULIN 317E. Bayer, G. Panhaus and M. Ali Khan

61. AUTOMATIC PEPTIDE SYNTHESIZER USEFUL FOR MULTIPLE PEPTIDESYNTHESIS AND PEPTIDE LIBRARIES 319

Ivo Blaha, Martin Flegel, Vera Cerna, Manfred Pavlfk,Vft Pokorny,Petr Mudra, Ludek Lepsa and Karel Zenfsek

62. CYCLIC PEPTIDE SYNTHESIS VIA DISULFIDE BONDS IN GOOD YIELD ANDPURITY - USE OF THE AIR OXIDATION/DIFFUSION METHOD 321

Graham B. Bloomberg, David Askin and Michael J.A. Tanner

63. IMPROVED SYNTHESIS OF DIFFICULT SEQUENCES CONTAINING SERINE ANDTHREONINE WITH FMOC CHEMISTRY 323

Graham B. Bloomberg, William J. Mawby and Michael J.A. Tanner

64. SOLID PHASE COUPLING OF UNPROTECTED REDUCING CARBOHYDRATESTO THE N-TERMINUS OF PEPTIDES 327

Ulrik Boas, Peter Heegaard and Mogens H. Jakobsen

65. ANALYSIS OF THE ANTIGENIC STRUCTURE OF TWO IMMUNODOMINANTREGIONS OF THE 16 KDA PROTEIN OF M. TUBERCULOSIS: ELUCIDATION OFTHE MINIMAL SIZE OF T CELL EPITOPES 329

Katalin A. Bogdan, Martin H. Vordermeier, Stipo Jurcevic, Juraj Ivanyiand Ferenc Hudecz

66. SOLUTION STRUCTURE OF THE GLA DOMAIN OF CLOTTING FACTOR VII BYCIRCULAR DICHROISM; CORRELATION WITH INHIBITORY PROPERTIES 323

P. Byfield, B. Bolgiano, C. Hyde, D. Martin and E. Tuddenham

xiii

67. LARGE-SCALE SOLID-PHASE CONTINUOUS-FLOW PREPARATION OFA 26-MER PEPTIDE THROMBIN INHIBITOR 335

Valerio Caciagli, Franco Cardinali, Fabio Bonelli and Paolo Lombardi

68. SYNTHESIS AND CHARACTERIZATION OF A COMBINATORIAL LIBRARY:APPLICATION TO THE DISCOVERY OF A BRADYKINTN B2 RECEPTORANTAGONIST 339

Sarvajit Chakravarty, Babu J. Mavunkel, Robin Andy and Donald J. Kyle

69. USE OF REDUCED («P[CH2-NH]) AND N-METHYL(vF[CO-N(Me)])PSEUDOPEPTIDES IN BACKBONE SCANNING OF T CELL EPITOPE 341

J. Cotton, A. Lecoq, M. Herve, B. Maillere, S. Leroy and A. Menez

70. NEW APPLICATION OF THE SYNTHETIC BRANCHED MULTIMERICPEPTIDES : MIME OF THE PHYSICOCHEMICAL PROPERTIES OFAPOLIPOPROTEIN A-I , 343

L. Demoor, C. Boutillon, M. Rosseneu, J.C. Fruchart and A. Tartar

71. CHARACTERIZATION OF BINBING SITES OF FIBRIN SPECIFIC MONOCLONALANTIBODIES USING COTTON-BOUND COMBINATORIALPEPTIDE LIBRARIES 347

L. Doleckova, M. Pavlik, Z. Voburka, M. Rinnova, J. Suttnar and J.E. Dyr

72. N-ALKYLATED PEPTIDOMIMETIC COMBINATORIAL LIBRARIES 351Barbara Dorner, Jutta Eichler, Gregory M. Husar, John M. Ostreshand Richard A. Houghten

73. CARBOXAMIDE PROTECTION OF ASPARAGINE AND GLUTAMINE BY10,1 l-DIHYDRO-5H-DIBENZO[A,D]CYCLOHEPTEN-5-YL(SUB) AND5H-DIBENZO[A,D]CYCLOHEPTEN-5-YL(DBS) GROUPS 353

Harmut Echner and Wolfgang Voelter

74. IDENTIFICATION AND SYNTHESIS OF AN ASPARTIMIDE PEPTIDEMODULATING T CELL RECOGNITION OF A SYNTHETICPEPTIDE ANTIGEN , 359

Nicholas J. Ede, Weisan Chen, James McCluskey, David C. Jacksonand Anthony W. Purcell

75. GEL PHASE 13C-NMR MONITORING OF SOLID PHASE GLYCOSIDE SYNTHESISHans-Michael Eggenweiler and Ernst Bayer 363

76. AN APPRAOACH TO THE SYNTHESIS OF ARGININE CONTAINING ,,.. yNUCLEOPEPTIDES VIA MODIFIED PHOSPHOTRIESTER METHODOLOGY ..' 367

D. Filippov, N.J. Meeuwenoord, E. Kuhl-Yeheskiely, J.C.H.M. Wijkmans,G.A. van der Marel and J.H. van Boom

77. PREPARATION OF SYNTHETIC PEPTIDE LIBRARIES USING A MULTI COLUMNPARALLEL-FLOW MPS DEVICE 369

Laura Gazzerro, Massimo Pinori and Paolo Mascagni

xiv

78. 2,4-METHANO AMINO ACIDS, NOVEL CONSTITUENTS OF BIOACTIVEPEPTIDES: TUFTSIN AS A MODEL 373

Eytan Gershonov, Ruth Granoth, Esther Tzehovel, Yehiel Gaoniand Mati Fridkin

79. COMPARISON OF SEVERAL SULFURIZING REAGENTS FOR SYNTHESIS OFPHOSPHOROTHIOATE OLIGONUCLEOTIDES ON DIFFERENT SUPPORTS 377

Michael Gerster, Konrad Bleicher and Ernst Bayer

80. RATIONALLY DESIGNED DIVERSE NON-PEPTIDES: VARIOUSLY SUBSTITUTEDPIPERAZINE AND PIPERAZINEDIONE LIBRARIES TARGETED FOR THEDISCOVERY OF BRADYKININ AND OTHER G-PROTEIN COUPLEDRECEPTOR ANTAGONISTS 381

Val S. Goodfellow, Christopher P. Laudeman, J. Ivan Gerrity,Michael Burkhard, Eric Strobel and Don A. McLeod

81. A NEW SIDE-CHAIN ANCHORING STRATEGY FOR SOLID-PHASE SYNTHESISOF PEPTIDE ACIDS WITH C-TERMINAL CYSTEINE 385

Yongxin Han, Josef Vagner and George Barany

82. STUDIES ON MECHANISM OF PEPTIDE CARBOXY ACTIVATION 389Christiane Hanay, Michael Beyermann and Peter Henklein

83. NEW LIGANDS FOR THE HUMAN MELANOMA MSH RECEPTOR IDENTIFIEDBY A PEPTOID LIBRARY (OLIGO N-SUBSTITUTED GLYCINES) 391

Gerhard Heizmann, Heidi Tanner and Alex N. Eberle

84. p-(5-DIBENZOSUBERENYL-5-HYDROXY)-BENZOIC ACID: A NEW LINKERFOR PEPTIDE SYNTHESIS 395

Bernd Henkel and Ernst Bayer

85. SYNTHESIS OF TRIPLE-HELICAL PEPTIDES INCORPORATING NATIVECOLLAGEN TYPE II SEQUENCES USING A CONTINUOUS FLOWSYNTHESIZER 399

W. Henkel, H. Echner, W. Voelter, U. Bahr and T. Vogl

86. SYNTHESIS, STRUCTURE AND BIOLOGICAL ACTIVITY OF CYCLICCCK-DERIVATIVES 403

Peter Henklein, Hardy WeiBhoff, Roland Kaufmann and Ute Schafer

87. NEW SAFETY-CATCH LINKAGES FOR THE DIRECT RELEASE OF PEPTIDEAMIDES INTO AQUEOUS SOLUTIONS 407

Stefan Hoffmann and Ronald Frank

88. DESIGN AND SYNTHESIS OF FMRF AMIDE-LIKE PEPTIDES AND THEIRAPPLICATION TO STUDY OF PAIN IN THE SPINAL CORD 411

Eagle Yi-Kung Huang, Jeff Bagust, Ram P.Sharma and Robert J. Walker

89. PHOTOCHEMICAL COUPLING OF PEPTIDES TO POLYSTYRENE MICROWELLPLATES 419

S0ren Peter Jensen, Svend Erik Rasmussen and Mogens Havsteen Jakobsen

xv

90. SOLID PHASE GLYCOPEPTIDE SYNTHESIS OF TYROSINE GLYCOSYLATEDGLYCOGENIN FRAGMENTS 423

Anita M. Jansson, Knud J. Jensen, Morten Meldal and Klaus Bock

91. SOLID PHASE SYNTHESIS OF Tn ANTIGENS IN BOTH FREE ANDIMMOBILIZED FORM 427

Jan Jezek, Jin Velek, Tomas Trnka and Martin Pisacka

92. HORNER-WADSWORTH-EMMONS ALKENE SYNTHESIS ON SOLID PHASEMONITORING BY 31P GEL PHASE NMR 429

Charles R. Johnson and Birong Zhang

93. DIFFICULT PEPTIDE SEQUENCES OF MMIF IN FMOC-CONVERGENT SOLIDPHASE PEPTIDE SYNTHESIS 431

Thomas Kaiser and Wolfgang Voelter

94. FORMATION OF DISULFIDE BOND ON SOLID SUPPORT 435Koichi Kawasaki, Yasuhiro Izuno, Masa Kakiuchi and Mitsuko Maeda

95. USE OF A TENTAGEL SUPPORT IN THE PREPARATION OF ALL SIXTEEN2'-DEOXYDINUCLEOSIDE PHOSPHORODITHIOATES 437

Jan Kehler, Anne B. Eldrup, Jakob Felding and Otto Dahl

96. C-TERMINAL SEQUENCE ANALYSIS OF PEPTIDES 441Weiland Keilholz, Stefan Stevanovic, Daniele Arnoldand Hans-Georg Rammensee

97. MYRISTYLATED NEF PEPTIDE (2-57) FROM HIV TYPE I: SYNTHESIS ANDSTRUCTURAL STUDIES 445

Roland Kellner, Stephan Rawer, Matthias Geyer and Hans R. Kalbitzer

98. THE IDENTIFICATION OF A NON-PEPTIDE GPHB/HIA ANTAGONIST 449J. Kitchin, J. Broomhead, B. Carter, A.J. Crame, M. Foster, M. Hann,E. Hornby, S. Hindley, C. Perry, A.J. Pipe, N.R. Taylor and P. Ward

99. OPTIMIZED PURITY CONTROL OF SYNTHETIC OLIGODEOXYRIBO-NUCLEOTIDES BY CAPILLARY ELECTROPHORESIS FORCLINICAL PCR ASSAY 455

Rainer Lehmann, Mattais Koch, Gerald Griibler, Wolfgang Reinig,Hans Zimmerman, Waleri Gross and Wolfgang Voelter

100. AN EFFICIENT THREE DIMENSIONAL ORTHOGONAL STRATEGY FORSOLID-PHASE SYNTHESIS OF A BIFUNCTIONAL PEPTIDE 459

Dominique Lelievre, David Daguet, Friedrich Piller, Veronique Piller,Cecille Vassard and Andre Brack

101. HSV-2 UNIQUE PEPTIDES WITHOUT SEROLOGICAL CROSS-REACTIVITY 461Ulla Ruden, Michael Levi and Britta Wahren

102. SOLID PHASE POLYAMINE CHEMISTRY - A ROUTE TO ANTI-TRYPANOSOMAL COMPOUNDS 463

Ian R. Marsh and Mark Bradley

xvi

103. SELECTION OF PROTEINASE INHIBITORS FROM A CONFORMATIONALLY-CONSTRAINED COMBINATORIAL PEPTIDE LIBRARY 465

Jeffrey D. McBride, Neil Freeman, Gonzalo J. Domingoand Robin Leatherbarrow

104. THE IMPORTANCE OF PEPTIDE SOLVATION IN THE SYNTHESIS OF A PEPTIDEANALOGUE OF THE 2A REGION OF THE FOOT AND MOUTH DISEASE VIRUSGENOME SHOWN BY CONDUCTIVITY MONITORING 469

Brendan McKeown, David J.S. Guthrie, Neil V. McFerran,Martin D. Ryan and Brian Walker

105. COMPARATIVE STUDIES OF METHOXY-SUBSTITUTED 4-BENZYLOXY-TRITYLAMINE LINKERS FOR SOLID PHASE SYNTHESIS OFPROTECTED PEPTIDE AMIDES 473

Mark Meisenbach and Wolfgang Voelter

106. SOLID PHASE SYNTHESIS OF PEPTIDE FRAGMENTS OF HUMAN RELAXINFOR THE ISOLATION OF SPECIFIC ANTIBODIES 477

Mark Meisenbach, Franz-Paul Armbruster, Stephan Becker,Theodor H. Lippert, Gerd Paulus, Hans-Jiirgen Kohlbau,Gerald Griibler and Wolfgang Voelter

107. RAPID SYNTHESIS OF FULLY PROTECTED PEPTIDE AMIDES 481M. Mergler and R. Nyfeler

108. SYNTHESIS OF SAPECIN EMPLOYING REGIOSELECTIVE DISULPHIDE BONDFORMATION 485

M. Mergler and R. Nyfeler

109. SOLID PHASE SYNTHESIS OF ENDOTHIOPEPTIDES USING 3-(N-a-BOCAMINOTHIOACYL)-l,3-THIAZOLIDINE-2-THIONES, NEW EFFICIENTTHIOACYLATING AGENTS 487

Robert J. Michelot, Hoang-Thanh Le and Michel Mayer

110. ANTISERA DIRECTED AGAINST SYNTHETIC PEPTIDES RECOGNIZE THENATIVE CCK-A RECEPTOR 489

Corinna Morys-Wortmann, Laurence J. Miller, Klaus Nebendahland Wolfgang E. Schmidt

111. A NOVEL STRATEGY FOR THE SYNTHESIS OF HEME-PEPTIDECONJUGATES : 491

Flavia Nastri, Angela Lombardi, Ornella Maglio, Giancarlo Morelli, GabbriellaD'Auria, Carlo Pedone and Vincenzo Pavone

112. SIDE REACTIONS ASSOCIATED WITH PHOSPHOPEPTIDE SYNTHESIS 495Elizabeth A. Ottinger, Quighong Xu andGeorge Barany

113. SPATIALLY ADDRESSABLE LIGATION ASSAYS: APPLICATION OFOLIGONUCLEOTIDE ARRAYS TO DNA FINGERPRINTING 499

Clare E. Pritchard and Edwin M. Southern

114. GLYCOPEPTIDE SYNTHESIS OF GPIIb (843-854) AND BOVINEFETUIN (152-164) 503

Stephan Rawer, Knut Adermann and Wolf-Georg Forssmann

115. LIPOSOMES AS CARRIERS FOR PEPTIDES IN CANCER THERAPY 505Francesca Reig, Isabel Haro, Liuis A. Lopez Barcons, E. Grieraand Angels Fabra

116. USE OF METHYL RED IN SOLID PHASE SYNTHESIS 509Marketa Rinnova, Martin Fusek and Michal Lebl

117. STRUCTURE-AFFINITY STUDIES OF CYCLIC DODEKAPEPTIDE ANALOGUESOF NEUROPEPTIDE Y 511

B. Rist, H.A. Wieland, K-D. Willim and A.G. Beck-Sickinger

118. CYCLIZATIONS OF PEPTIDES AND OLIGOAMIDES BOUND TO SILICA GELAS A RIGID SUPPORT 515

M. Rothe, A. Negele, T. Mohr and S. Kneer

119. PSEUDO-PROLINES IN PEPTIDE SYNTHESIS: TEMPORARY TURN INDUCTIONAND CONFORMATIONAL RESTRICTION 519

Declan Ryan, Pascal Dumy, Ian M. Eggleston and Manfred Mutter

120. DE NOVO LEAD IDENTIFICATION AGAINST GLYCOSOMALPHOSPHOGLYCERATE KINASE 523

Isabell Samson, Arthur Van Aerschot, Bart Samyn, Jozef Van Beeumenand Piet Herdewijn

121. DIESTER BUILDING BLOCKS OF pSER AND pTHR SUITABLE FOR FMOCSOLID PHASE PEPTIDE SYNTHESIS 525

Holger Schmid, Stefan Vetter, Willi Bannwarth and Eric Kitas

122. MATRIX-DEPENDENT DEPROTECTION OF PEPTIDE FRAGMENTS DURINGMALDI-TOF MASS SPECTROMETRY 529

Margit Schmidt, Eberhard Kraus, Michael Beyermann and Michael Bienart

123. USE OF THE Hmb BACKBONE PROTECTING GROUP IN THE SYNTHESIS OFDIFFICULT SEQUENCES 533

Robin G. Simmonds

124. NOVEL HANDLES FOR SOLID PHASE SYNTHESIS OF PEPTIDEN-ALKYLAMIDES 537

Michael F. Songster, Josef Vagner and George Barany

125. SYNTHESIS AND FOLDING OF co-CONOTOXINS 539Linda Thomas, Paul F. Alewood and Richard J. Lewis

126. SYNTHESIS OF NEW CHIRAL PNA ANALOGUES 543A.C. van der Laan, I. van Amsterdam, R.S. Oosting, R. Brands,N.J. Meeuwenoord, E. Kuyl-Yeheskiely and J.H. van Boom

xvm

127. PROTECTED PEPTIDE INTERMEDIATES USING A TRITYL LINKER ONA SOLID SUPPORT 545

Alexandra van Vliet and Godefridus I. Tesser

128. SOLID PHASE SYNTHESIS OF [4/Pro-7]SARAFOTOXIN-S6b APPLYINGTHE CONCEPT OF PSEUDO-PROLINES 549

Frank Wahl, Barbara Rohwedder, Nathalie Berclaz and Manfred Mutter

129. TOPOGRAPHICAL MIMICS OF A STRUCTURED PEPTIDE SELECTED FROMA CONFORMATIONALLY-HOMOGENEOUS PEPTIDE COMBINATORIALLIBRARY 553

Andrew Wallace, Elisabetta Bianchi, Michael Houston, Robert Hodgesand Antonello Pessi

130. PREPARATION OF PHOSPHOSERINE, THREONINE AND TYROSINECONTAINING PEPTIDES BY THE FMOC METHODOLOGY USING PRE-FORMEDPHOSPHOAMINO ACID BUILDING BLOCKS 557

P. White and J. Beythien

131. JV-DITHIASUCCINOYL (DTS)-AMINES: NOVEL SULFURIZING REAGENTSFOR THE SOLID PHASE PREPARATION OF THIOPHOSPHOPEPTIDES ANDOLIGODEOXYRIBONUCLEOSIDEPHOSPHOROTHIOATES 561

Qinghong Xu, Karin Musier-Forsyth, Robert P. Hammer and George Barany

132. INTRAMOLECULAR DISULFIDE BOND FORMATION ON THE SOLID SUPPORT:SYNTHESIS OF RGDF-CONTAINING CYSTINE PEPTIDES 565

Yasuo Yamamoto and Shosuke Sofuku

133. PEPTIDE ENGINEERING FOR VACCINES THROUGH POLYOXIMECHEMISTRY : '. 567

Weiguang Zeng, Keith Rose and David C. Jackson

134. SOLID PHASE SYNTHESIS OF THE FULLY PROTECTED NEPHRITOGENOSIDEGLYCOPEPTIDE 573

Hong Zhang, Yali Wang and Wolfgang Voelter

Abbreviations 575

Author Index 578

Subject Index 583