Peptides. Chemistry and Biology. Proceedings of the Tenth American Peptide Symposium. May 23-28, 1987, St. Louis, Missouri, U.S.A. Garland R.

Peptides Chemistry and Biology Proceedings of the Tenth American Peptide Symposium May 23-28, 1987, St. Louis, Missouri, U.S.A. Edited by Garland R. Marshall Department of Pharmacology Washington University School of Medicine St. Louis, Missouri 63110, U.S.A. UN1VLIIC1T/TRP! HUOTHEK h.ai 'i'1 Jv'LR Ti:f>'ri;ocHr: INFORM/0VOr!Sb;EU.IQTHEK ESCOM Leiden 1988

Preface v Tenth American Peptide Symposium Committees viii Sponsors, Donors and Contributors ix Abbreviations x Sixth Alan E. Pierce Award Lecture Naturally occurring active peptides from anterior pituitary and gonads 3 C.H.Li Session I: Conformation of peptides Circular dichroism measurement of peptide helix unfolding 15 K.R. Shoemaker, R. Fairman, E.J. York, J.M. Stewart andr.l. Baldwin Theoretical studies of protein structure 21 F.E. Cohen and I.D. Kuntz Solution structures of defensins: Naturally occurring peptide antibiotics 27 A.C. Bach II, X.-L. Zhang, D.R. Hare and A. Pardi Action of alanine-rich antifreeze polypeptides: Dipole moment of a- 32 helix for ice recognition A. Chakrabartty, C.L. Hew, D. Yang and M. Sax Conformational analysis of a cyclic hexapeptide by rotating frame NOE 35 (ROE) evaluation and molecular dynamics (MD) calculations H. Kessler, K. Wagner and M. Will 13C NMR T, studies and enantiotopomerisations of 3l0-helical poly- 37 peptides G. Jung, R.-P. Hummel, K.-P. Voges, K. Albert and C. Toniolo xv

The conformation of oxytocin bound to neurophysin I 39 K. Hallenga, N.R. Nirmala, D.D. Smith and V.J. Hruby Conformational analysis of human atrial natriuretic polypeptide by 42 NMR and distance geometry algorithm Y. Kobayashi, T. Ohkubo, Y. Kyogoku, S. Koyama, M. Kobayashi and N. Go The structure of a new hexameric form of human insulin 44 G.D. Smith, D.C. Swenson, Z. Derewenda, E.J. Dodson, G.G. Dodson, CD. Reynolds and K. Sparks Comparative 2D NMR studies of the Phe B24 -* insulin Leu mutant human 47 M.A. Weiss, E. O'Shea, K. Inouye, B.H. Frank, I. Khait, D. Nguyen, L.J. Neuringer and S.E. Shoelson Hexapeptide metal binding domains in proteins 51 H.A. Anderson, M.A. Eastman, L.G. Pedersen, R.G. Hiskey and A.T. Hagler Conformation of the flap of human renin 54 J.A. Fehrentz, A. Heitz, F. Heitz, C. Carelli, F.X. Galen, P. Corvol andb. Castro Isotope-filtered proton NMR experiments for the conformational de- 57 termination of peptides in solution and bound to biomacromolecules S.W. Fesik, R.T. Gampe, Jr., E.T. Olejniczak, J.R. Luly, H.H. Stein and T. W. Rockway Modulation of membrane morphology by basic proteins and polypep- 60 tides P.E. Fraser and CM. Deber An application of distance geometry in the modeling of peptides: A 62 molecular complex of the aglycon of aridicin A J.C. Hempel, L. Mueller, S.L. Heald and P.W. Jeffs Vibrational circular dichroism of polyproline 65 R. Kobrinskaya, S. C. Yasui and T.A. Keiderling Conformational mobility in the vasopressin series 68 C.W. DeBrosse, J.C. Hempel and K.D. Kopple xvi

Conformation and motion of biologically active peptides as bound to 71 phospholipid membrane A. Milon, K. Wakamatsu, K. Saito, A. Okada, T. Miyazawa and T. Higashijima Two-dimensional NMR and computer modeling studies of two con- 74 formers of an actinomycin-related peptide lactone A.B. Mauger, J.A. Ferretti, K.S. Gallagher andj.v. Silverton 2D NMR evaluation of 3D structure of scorpion Buthus eupeus neu- 77 rotoxin M, in solution V.S. Pashkov, N. A. Hoang, V.N. Maiorov and V.F. Bystrov 'H NMR and CD studies of tfes-trp1, Nle12-rninigastrin in H20/TFE 79 N.J. Mammi, S. Mammi and E. Peggion Conformational analysis of 5,5-dimethylthiazolidine-4-carboxylic acid 81 (Dtc), a readily available proline analog /. Samanen, T. Cash, D.S. Eggleston andm. Saunders Conformational analysis of model cyclic endothiopeptides by NMR and 84 molecular modeling techniques D.B. Sherman, R.A. Porter and A.F. Spatola Peptide inhibitor binding to bacterial collagenase by proton NMR 87 relaxation studies: A direct approach to structure-activity relationships F. Toma, V. Dive and A. Yiotakis Vibrational circular dichroism of aromatic polypeptides 90 S. C. Yasui and T.A. Keiderling Crystal and molecular structure of S-deoxo [y(r) hydroxy-ile3]-amanin: 93 amide: A synthetic analog of Amanita toxins G. Zanotti, T. Wieland, E. Benedetti, B. Di Blasio, V. Pavone and C. Redone Session II: Peptide mimetics Design and comparison of nonpeptide and peptide CCK antagonists 97 R.M. Freidinger, P.S. Anderson, M.G. Bock, R.S.L. Chang, R.M. DiPardo, B.E. Evans, V.M. Garsky, and W.L. Whitter V.J. Lotii, K.E. Rittle, D.F. Veber xvn

On the importance of the peptide bonds in the C-terminal tetrapeptide 101 of gastrin and in the C-terminal heptapeptide of cholecystokinin M. Rodriguez, P. Fulcrand, M.-F. Lignon, M.-C. Galas, J.-P. Bali, R. Magous, P. Dubreuil, J. Law and J. Martinez Reverse turn mimics 105 W.F. Huffman, J.F. Callahan, D.S. Eggleston, K.A. Newlander, D.T. Takata, E.E. Codd, R.F. Walker, P.W. Schiller, C. Lemieux, W.S. Wire and T.F. Burks Nonpeptide mimetics of jaspamide 109 M. Kahn and T. Su trans Carbon-carbon double bond isosteres of the peptide bond: General 112 methodology and the synthesis of cholecystokinin (CCK) analogs Y.K. Shue, G.M. Carrera, Jr., A.M. Nadzan, J.F. Kerwin, H. Kopecka and C. W. Lin Conformations of cholecystokinin and their relationships to rigid 115 molecules R.A. Hughes and P.R. Andrews Acyl lysinamido phosphonates: Potent, long-acting inhibitors of an- 118 giotensin-converting enzyme M.J. Loots, M.C. Badia, D.W. Cushman, J.M. DeForrest, D.S. Karanewsky, M.G. Petri, E.W. Petrillo, Jr. and J.R. Powell Diaminoalcohols and diaminoketones: Potent inhibitors of an enke- 120 phalin-degrading rat brain aminopeptidase N.G. Delaney, E.M. Gordon, M.M. Asaad, D. W. Cushman, D.E. Ryono, R. Neubeck and S. Natarajan Synthesis of conformational^ constrained CCK-4 analogs containing 123 a substituted gamma lactam ring D.S. Garvey, P.D. May and A.M. Nadzan A dehydro-keto-methylene inhibitor of substance P degradation 126 A. Ewenson, R. Laufer, J. Frey, E. Rosenkovich, M. Chorev, Z. Selinger and C. Gilon Synthesis and properties of some peptides related to the bicyclic 8-129 turn dipeptide (BTD) U. Nagai, R. Kato, K. Sato, N. Ling, T. Matsuzaki and Y. Tomotake Tripeptide aminoalcohols: A new class of human renin inhibitors 131 S. Natarajan, C.A. Free, E.F. Sabo, J. Lin, E.R. Spitzmiller, S.G. Samaniego, S.A. Smith andl.m. Zanoni xvui

Synthesis and antagonist activities of backbone-modified angiotensin 134 II analogs W.H. Roark, F.J. Tinney and E.D. Nicolaides A position seven analog of angiotensin II with potent antagonist activity 137 J. Samanen, J. C. Hempel, D. Narindray and D. Regoli Session III: Analytic and synthetic methods Asymmetric synthesis of amino acids 143 D.A. Evans, A.E. Weber, T.C. Britton, J.A. Ellman and E.B. Sjogren Asymmetric syntheses of /3-OH and /3-OH, 7-alkyl Analogs of the unusual cyclosporin amino acid MeBmt R.D. Tung, C.-Q. Sun, D. Deyo and D.H. Rich a-arnino acids: 149 Activation and racemization in peptide bond formation 152 N.L. Benoiton andf.m.f. Chen Development of methodology for arginine and jv*-alpha protection in 157 peptide synthesis R. Ramage, J. Green and M.R. Florence Solid phase synthesis of C-terminal peptide amides under mild conditions 159 F. Albericio, N. Kneib-Cordonier, L. Gera, R.P. Hammer, D. Hudson and G. Barany Total synthesis of porcine and human cholecystokinin-33 (CCK-33) by 162 the classical solution procedure Y. Kurano, T. Kimura and S. Sakakibara Simultaneous multiple peptide synthesis: The rapid preparation of large 166 numbers of discrete peptides for biological, immunological, odological studies R.A. Houghten, J.H. and meth Cuervo, J.M. Ostresh, M.K. Bray and N.D. Frizzell Synthesis and characterization of peptides and proteins 173 S.B.H. Kent, K.F. Parker, D.L. Schiller, D.D.-L. Woo, I. Clark-Lewis andb.t. Chait Chiral synthesis of D-a,w-diaminoalkanoic acids 179 P.L. Beaulieu and P. W. Schiller Synthesis of anglerfish peptide YG (APY) 181 A. Balasubramaniam, D.F. Rigel, P. C. Andrews, J.E. Dixon, R.L. Jackson andj.e. Fischer xix

A mild and novel approach containing peptides during the SN2 deprotection step R.H. Berg, A. Holm and J.P. Tarn to sulfation of serine- and threonine- 184 Synthesis of an e(7-glu)lys cross-linked peptide in human fibrin 187 M.S. Bernatowicz, C.E. Costello and G.R. Matsueda Use of Fmoc amino acid chlorides in peptide synthesis 189 M. Beyermann, L.A. Carpino D. Granitza, M. Bienert, B. Mehlis, H. Niedrich and Studies of acetamidomethyl as cysteine protection: Application in 192 synthesis of ANF analogs S.F. Brady, W.J. Paleveda and R.F. Nutt Analysis and enantiomeric resolution of a-alkyl-a-amino acids 195 H. Bruckner, I. Bosch, S. Ktihne and S. Zivny Automated Fmoc synthesis on polystyrene resins 198 H. Beilan, D.L. Noble, C.P. Ashton and D.P. Hadfield Chemical synthesis of human epidermal growth factor (EGF) and human 202 type a transforming growth factor (TGFa) R. DiMarchi, E. Osborne, E. Roberts and L. Slieker Design, construction and application of an automated large scale solid 204 phase peptide synthesizer: Large scale preparation of vasopressin analogs M.S. Edelstein, J.L. Hughes, P.K. Bhatnagar, J.E. Foster, K.D. Tubman, S. Kalbag, A. Patel, P. Voelker, D. Narindray, A.R. Culwell and M. Sherlund Solid phase synthesis using high-titer resins 208 M.S. Edelstein, J.L. Hughes, J.E. Foster and A.R. Culwell Rapid solid phase peptide synthesis on a controlled pore glass support 210 K. Buttner, H. Zahn and W.H. Fischer Solid phase peptide synthesis using BOP reagent: Synthesis of growth 212 hormone releasing factor (GRF) analogs A. Fournier, C.-T. Wang and A.M. Felix Continuous flow peptide synthesis 215 7?. Frank, H. Leban, M. Kraft and H. Gausepohl Two new disulfide bonding reactions for the synthesis of cystine peptides 217 N. Fujii, A. Otaka, O. Ikemura, T. Watanabe, H. Aral, S. Funakoshi and H. Yajima xx

Kinetics of coupling reactions in solid phase peptide synthesis 220 B. Hetnarski and R.B. Merrifield The utility of reductive alkylation in solid phase peptide synthesis 223 S.J. Hocart, N. Y. Jiang, M. V. Nekola and D.H. Coy A novel approach to the purification of peptides by reversed-phase HPLC: Sample displacement chromatography 226 R.S. Hodges, T.W.L. Burke and C.T. Mant A deprotection method using tetrachlorosilane-trifluoroacetic acid sea- 229 vengers by a 'reductive acidolysis' mechanism: Application to the synthesis of a novel tachykinin peptide, scyliorhinin I Y. Kiso, M. Yoshida, T. Kimura, T. Mimoto, M. Shimokwa and T. Fujisaki Studies related to the syntheses of pseudobactin 232 T. Kolasa and M.J. Miller Chlorotrimethylsilane-phenol as a selective deprotection reagent for the 236 zer/-butyloxycarbonyl group E. Kaiser, Sr., P.M. Kubiak, J.P. Tarn and R.B. Merrifield Synthesis of peptides containing a,a-disubstituted amino acids: Experi- 239 ments related to a,a-diethylglycine M. T. Leplawy, K. Kaczmarek and A. Redlinski Carboxyl-terminal peptide degradation: Formation of a C-terminal 242 derivative J.B. Stimmel and G.M. Loudon On-resin biotinylation of a human interleukin-1 beta analog convenient one-step purification M.R. Deibel, T.J. Lobl, A. W. Yem, D.E. Tracey and J. W. Paslay and its 245 Synthetic and physicochemical studies of benzhydrylamine resins with 249 different substitution levels: Implications for solid phase peptide syn thesis C.R. Nakaie, R. Marchetto, S. Schreier and A. CM. Paiva Preparation of protected peptides by the solid phase method and HF- 252 stable, but easily removable, blocking groups W. Neugebauer, G. Champagne, M.-R. Lefebvre ande. Escher xxi

Application of trimethylsilyl trifluoromethanesulfonate deprotection 255 procedure for solid phase peptide synthesis M. Nomizu, Y. Inagaki, K. Asano, TV. Fujii, O. Ikemura, A. Otaka andh. Yajima Improved linker resin combination for solid phase peptide synthesis 259 M. Mergler, R. Nyfeler, J. Gosteli and P. Grogg Solid phase synthesis of acid-sensitive peptide amides 261 B. Penke, W. Gray, C.A. Hoeger and J. Rivier Structure-function relationships in the anemone Stichodactyla helianthus 264 neurotoxin I: Synthesis of native sequence and Glu 8 to Gin analog M. W. Pennington, W.R. Kern andb.m. Dunn Use of Fmoc amino acid oxobenzotriazine esters in continuous flow 267 low pressure solid phase peptide synthesis E. Atherton, J.C. Glass, B.H. Matthews, G.P. Priestley, J.D. Richards, P.W. Sheppardand W.A. Wade Protection of histidine in peptide synthesis: A reassessment of the trityl 270 group P. Sieber and B. Riniker A method for solid phase peptide synthesis (SPPS) of C-terminal sulfonic 273 acid peptides: Synthesis of taurinel6-gramicidin A R. W. Roeske and T.P. Hrinyo-Pavlina Preparation of new amino acids 276 Y. Herve, D.H.R. Barton, J. Thierry and P. Potier Protease-catalyzed synthesis of oxytocin 279 P. Thorbek, J. Lauridsen and F. Widmer Protection of side-chain alcoholic hydroxyl groups of serine and threo- 282 nine by the dimethylphosphinyl (Dmp) group M. Ueki, M. Saito and H. Oyamada Frhoc-polyamide continuous flow solid phase synthesis of a 74-residue 284 fragment of human /3-chorionic gonadotropin C.-R. Wu, V.C. Stevens, G.W. Tregear and J.D. Wade Synthesis of human secretin 287 G. Wendlberger, W. Gbhring, G. Hubener, R. Scharf, J. Beythien, Ch. Beglinger and E. Wiinsch xxn

Regiospecific synthesis of [13C-2]-(2S, SSW/ww-epoxysuccinyl-L-leucyl- 289 isoamylamide Y. Yabe and D.H. Rich Convenient synthesis of 2-methyl-3-phenylserine, a sterically hindered 292 a, a-disubstituted amino acid /. Zabrocki, Z. KaminskiandM.T. Leplawy Session IV: Mechanism of action Inositol phosphates and calcium signaling 297 M.J. Berridge The insulin receptor: A hormone-activated transmembrane tyrosine 302 kinase comprised of two large independently folded soluble domains L. Ellis Perturbation-free modification and analysis residues of a membrane protein M. Engelhard, B. Hess and F. Siebert of functional amino acid 308 Wasp venom toxin mastoparan, a histamine releaser from mast cells, 310 is a direct activator of GTP-binding regulatory proteins T. Higashijima, S. Uzu, T. Nakajima and T. Miyazawa Role of the signal sequence in protein secretion 313 L.M. Gierasch, M.S. Briggs and C.J. McKnighi Membrane-catalyzed molecular mechanism of tachykinin receptor se- 318 lection R. Schwyzer, D. Erne, K. Rolka, J. W. Bean and D.F. Sargent Synthetic peptides identify a critical lysine residue in the SV-40 nuclear 321 transport signal P. Kanda, R. C. Kennedy and R.E. Lanford Studies on synthetic peptides of small subunit of ribulose 1,5-bisphos- 323 phate carboxylase (RuBisCO) J.V. Edwards, J.M. Bland, D.G. Cornell, T.E. Cleveland, S. Landry and S. G. Bartlett Biophysical studies of the fragments of the extension peptide of cy- 325 tochrome P-450 (SCC) precursor H. Aoyagi, S. Lee, H. Mihara, T. Kanmera and T. Kato xxiii

Binding of dynorphin-a-(l-13) and some N-terminal fragments neutral lipid bilayer membranes J. W. Bean, D. Erne, D.F. Sargent and R. Schwyzer to 328 Membrane-adjacent regions of receptor proteins 330 CM. Debet; C.J. Brand!, R.B. Deber, L.C. Hsu andx.k. Young Ionic interactions between substrate side chains and individual subsites 332 in the pepsin active site J. Pohl and P.M. Dunn Relationship between the antiviral activity of peptides and the stabi- 335 lization of membrane bilayers R.M. Epand, R.C. McKenzie, D.C. Johnson, T.J. Maggiora andm. W. Wathen Lobl, H.E. Renis, L.L. Direct 13C NMR observation of a tetrahedral species in the binding 338 of a peptidyl ketone pseudosubstrate to penicillopepsin, a fungal aspartic proteinase J. Maibaum, M.K. Dhaon, P.G. Schmidt, M. Oka andd.h. Rich Activities of glucagon antagonists on normal liver: Evidence for camp- 341 independent events R.L. McKee, D. Trivedi, C. Zechel, D. Johnson, K. Brendel and V.J. Hruby Crystal structure of the covalent complex formed by a peptidyl a,a- 344 difluoro-/3-keto amide with porcine pancreatic elastase at 1.78 A re solution L.H. Takahashi, R. Radhakrishnan, E.F. Meyer, Jr. and D.A. Trainor Session V: Protein design/engineering Synthetic proteins with a new three-dimensional architecture 349 M. Mutter Sequence simplification and randomization and the design of peptide 354 recognition surfaces I. Chaiken, S. Ando, G. Fassina and Y. Shai A semisynthetic approach to protein engineering: Interleukin-2 rede- 364 signed T.L. Ciardelli, F.E. Cohen, R. Gadski, L. Butler, B. Landgraf and K.A. Smith xxiv

The role of cysteine residues in interleukin-3 function established by 366 total chemical synthesis of analogs /.' Clark-Lewis, L.E. Hood and S.B.H Kent Cooperativity in multiple amphipathic helical domains of apolipoprotein 369 A-I J.P. Segrest, A. Gawish, M. Iqbal, C.G. Brouil/ette, K.B. Gupta and G.M. Anantharamaiah Semisynthesis of a deletion mutant of cytochrome c by condensation 372 of enzymatically activated fragments C.J.A. Wallace and A.E.I. Proudfoot Characterization of a two-chain structural variant ofrecombinant human 376 growth hormone E. Canova-Davis, LP. Baldonado, L.J. Basa, R. Chloupek, T. Doherty, R.J. Harris, R.G. Keck, M.W. Spellman. W.F. Bennett and W.S. Hancock Reoxidation of basic reduced insoluble proteins: Example of neurotoxin 379 II of the scorpion Androctonus australis Hector J.M. Sabatier, H. Darbon, P. Fourquet, H. Rochat and J. van Rietschoten Trypsin-catalyzed coupling of synthetic peptides: Semisynthetic produc- 381 tion of phospholipase A2 mutants in high yield /. van Binsbergen, A.J. Slotboom and G.H. de Haas Protein engineering: Design and synthesis of betabellin 7 383 S.B. Daniels, P.A. Reddy, E. Albrecht, J.S. Richardson, D.C. Richardson andb.w. Erickson Phospholipid organization and motion in the presence of model am- 386 phipathic helix-forming peptides with opposite distribution of charges R.M. Epand, M. Iqbal, A. Gawish, J.P. Segrest, W.K. Surewicz and H.H. Mantsch G.M. Anantharamaiah, Simulation of the crystal of Streptomyces griseus protease A 389 D.H. Kitson, F. Avbelj, J. Synthesis Moult anda.t. Hagler and oxidative properties of cysteine-containing fragments of 392 bovine growth hormone S.R. Lehrman, T.F. Holzman, C.J. Cole andd.n. Brems The role of cysteine residues in human interleukin-ly3 396 Y. Masui, T. Kamogashira, Y.-M. Hong, Y. Hirai Y. Kikumoto, S. Nakai and XXV

Synthesis of two component models of elastin 399 K.U. Prasad, M. Iqbal and D.W. Urry Covalent semisynthesis of a-chain of hemoglobin: Protease-catalyzed 404 transpeptidation at the permissible discontinuity site A.S. Acharya, Y.J. Cho and G. Sahni Session VI: Nucleic acid/peptide interactions The structural basis for activation of trp repressor by L-tryptophan 411 R. W. Schevitz, R.-G. Zhang, C.L. Lawson, Z. Otwinowsky, A. Joachimiak and P.B. Sigler Interaction of peptide antibiotics with DNA 416 T.P. Lybrand Chemical synthesis of a retroviral nucleic acid binding protein 420 T.D. Copeland, L.E. Henderson, R. Gorelick, Y. Kim and S. Oroszlan Binding of a thynnine Z-l fragment to DNA 422 F. Marchiori, G. Borin and M. Palumbo Session VII: Structure-activity relations Details of the interaction of phosphorus-containing peptide inhibitors 427 with thermolysin P.A. Bartlett, D.H. Drewry, J.E. Hanson and C.K. Marlowe Design of bradykinin antagonists 433 J.M. Stewart andrj. Vavrek Vasopressin agonists and antagonists present distinct pharmacophores 438 at the renal V2 receptor M.L. Moore and W.F. Huffman Synthesis and airway smooth muscle relaxant activity of linear and cyclic 441 vasoactive intestinal peptide analogs D.R. Bolin, 7.-7. Sytwu, J.M. Cottrell, R.J. Garippa, M. O'Donnell C.C. Brooks and Structure-activity studies of atrial natriuretic factor 444 R.F. Nutt, T.M. Ciccarone, S.F. Brady, CD. Colton, W.J. Paleveda, T.A. Lyle, T.M. Williams, D.F. Veber, A. Wallace and R.J. Winquist XXVI

Characterization of the interaction of thrombin with the C-terminal 447 region of the leech anticoagulant peptide hirudin J.L. Krstenansky, S.J.T. Mao, T.J. Owen andm.t. Yates Characterization of parathyroid hormone antagonists 449 L.H. Caporale, M. Chorev, J.J. Levy, C.T. Gay, J.E. Reagan, M. Rosenblatt andr.f. Nutt M.E. Goldman, P.A. DeHaven, Angiotensin II. Synthesis and biological activity of 8-(i? and S)- 452 tetrahydroisoquinoline and 1-(R and 5)-(proline)thiazole analogs P. Balasubramanian and G.R. Marshall NMR analysis and conformational characterization of cyclic antagonists 457 of gonadotropin-releasing hormone E.L. Baniak II, L.M. Gierasch, J. Rivier and A.T. Hagler The a-mating factor of Saccharomyces cerevisiae: A lipopeptide? 459 F. Naider, P. Shenbagamurthi, S. Marcus and J.M. Becker Receptor-selective somatostatin (SRIF) analogs 462 D.H. Coy, M.L. Heiman, J. Rossowski, W.A. Murphy, J.E. Taylor, S. Moreau and J.-P. Moreau Synthesis and biological activity of novel linear and cyclic GRF analogs 465 A.M. Felix, C.-T. Wang, E. Heimer, A. Fournier, D.R. Bolin, M. Ahmad, T. Lambros, T. Mowles and L. Miller Weak oxytocin agonist converted to highly potent oxytocin antagonist 468 through bicyclization P.S. Hill, J. Slaninova and V.J. Hruby Synthesis and biological activity of dicarba analogs of vasopressin 471 antagonists J.F. Callahan, W.F. Huffman, M.L. Moore, N.C.F. Yim, H.G. Bryan, K.A. Newlander, V. W. Magaard, F. Stassen, L. Kinter, G. Dytko, C. Albrightson, B. Brickson, N. Caldwell, G. Heckman and D. Schmidt Renin inhibitors based on novel dipeptide analogs: Increased efficacy 474 through systematic inclusion of polar functionality D.J. Kempf, E. de Lara, J.J. Planner, H.H. Stein, J. Cohen and H.D. Kleinert Tyrosine alone exhibits opiate-like activity when linked to an amphi- 476 pathic hydrocarbon chain M.A. Khaled, G.M. Anantharamaiah, J.M. Beaton and C.L. Watkins xxvn

Functional residues in atriopeptin (103-125)-amide 479 Y. Konishi, R.B. Frazier, G.M. Olins, D.J. Blehm, F.S. Tjoeng, M.E. Zupec and D.E. Whipple Tachykinin receptors 482 S. Lavielle, G. Chassaing, J. Besseyre, Marquet, J. C. Beaujouan, L. Bergstrom, S. Julien, D. Loeuillet, A. Y. Torrens and J. Glowinski Growth hormone-releasing factor analogs with potent antagonist activity 484 N. Ling, K. Sato, M. Hotta, T.-C. Chiang, H.-Y. Hu and M.-H. Dong Transition-state analog inhibitors of human renin 487 J.R. Luly, A.K.L. Fung, J.J. Planner, P.A. Marcotte, N. BaMaung, J.L. Soderquist and H.H. Stein Peptidyl amino steroids as potential new antiarrhythmic agents 490 M. Mokotoff, M. Zhao, Q.-J. Liao, L.K. Wong, W. Barrington and J. Elson Contribution of residues B26-B30 to the receptor binding affinities of 494 insulin analogs modified at position Al, A21 or B24 S.H. Nakagawa andh.s. Tager Development of selective agonists for substance P and neurokinins 497 receptors G. Drapeau, S. Dion, P. D'Orleans-Juste, N.-E. Rhaleb and D. Regoli Novel, subnanomolar renin inhibitors containing a postscissile site azide 500 residue S.H. Rosenberg, K.W. Woods, J.J. and J. Cohen Planner, H.H. Stein, H.D. Kleinert Structure-activity relationships of cholecystokinin-8 analogs: Compa- 503 rison of pancreatic, pyloric sphincter and brainstem CCK receptor activities with in vivo anorexigenic effects T.K. Sawyer, R.T. Jensen, T. Moran, P.J.K.D. Schreur, D.J. Staples, A.E. devaux and A. Hsi Synthesis and activity profiles of bivalent [Leu5]enkephalin-a-oxymor- 505 phamine hybrid opioid receptor ligands P.W. Schiller, T.M.-D. Nguyen, C. Lemieux, D.L. Larson, G. Ronsisvalle, A.E. Takemori and P.S. Portoghese Structure-function studies in a series of tachykinin antagonists containing 508 a conformationally constrained tryptophan analog B.A. Morgan, J. Singh, E. Baizman, H. Bentley, D. Keifer and S. Ward xxvni

Potent in vivo inhibitors of rat renin 510 J. Sueiras-Diaz, D.M. Jones, D.M. Evans, M. Szelke, BJ. Leckie, S.R. Beattie, E.C.H. Wallace and J.J. Morton Session VIII: Immunology Models and mechanisms for the immune recognition of protein antigenic 515 sites by B-cells and T-cells J.A. Smith A synthetic strategy for epitope mapping 519 H.M. Geysen, S.J. Rodda and T.J. Mason Solid phase synthesis of biologically active antigenic peptides for T- 524 cells LA. Casten, P. Kaumaya, M.S. Anderson, J.A. Smith and S.K. Pierce Recognition of peptide antigens by T-lymphocytes 527 B. Singh, M. Boyer, Z. Novak, E. Fraga and A. Fotedar Structure-function relationship in protection against foot and mouth 531 disease (FMD) by a synthetic peptide R. DiMarchi, G. Brooke, C. Gale and T. Doel Tubulin domains examined by antibodies from synthetic peptides 534 D. Andreu, S. de la Vina and J.M. Andreu Neutralizing rabbit antibodies to synthetic human interleukin-2 (IL- 537 2) peptides W. Danho, R. Makofske, J. Swistok, J. Michalewsky, Jenson, W.-H. Tsien and M. Gately T. Gabriel, J. Use of synthetic peptides for specific assays of proproteins: Assay proapolipoprotein A-I C. Martin, A. Barkia, J.C. Gesquiere, Fruchart and A. Tartar P. Puchois, C. Cachera, J.C. of 540 The determination of the precise amino acids involved, and their relative 543 importance, in peptide antigen/monoclonal antibody interactions R.A. Houghten, JR. Appel and J.M. Sitarik Synthesis of glycopeptides with tumor-associated antigen structure 547 H. Kunz, S. Friedrich-Bochnitschek and S. Birnbach xxtx

Formation of amphipathic secondary structure is correlated to T-cell 549 antigenicity in a series of synthetic peptides from sperm whale myoglobin L.R. Sanza, L.M. Gierasch, J.A. Berzofsky, G.K. Buckenmeyer, K.B. Cease and C.S. Ouyang Manipulation of the immune response against a peptide from the C- 551 terminal part of the surface protein VP1 of foot and mouth disease virus W.M.M. Schaaper, W.C. Puijk, D.J.A. Meijer, H. Lankhof, W.P.A. Posthumus andr.h. Meloen Mimicking protective epitopes of foot and mouth disease virus with 553 synthetic peptides A.Yu. Surovoy, O.M. Vol'pina, V.M. Gelfanov and V.T. Ivanov Characterization of antibody binding sites using peptides synthesized 555 on aminomethyl-resin W.-J. SyuandL. Kahan Session IX: Growth factors/oncogenes Structure-activity studies of transforming growth factor 561 J.P. Tarn Peptide substrates and inhibitors of TV-myristoyl transferase 566 S.R. Eubanks, D.S. Towery, F.S. Tjoeng, S.P. Adams, D.A. Towler, E. Jackson-Machelski, L. Glaser and J.L Gordon Analysis of the interaction of IGF I and structural mutants of IGF 570 I with the IGF types 1 and 2 and insulin receptors M.A. Cascieri, G.G. Chicchi, B.G. Green, J. Applebaum, N.S. Hayes and M.L. Bayne Conformational studies of N-terminal segments ofras p21 proteins 572 C.-H. Niu, K. Han and P.P. Roller Third loop analogs of epidermal growth factor: Bioassay studies for 575 receptor affinity and tyrosine kinase activation T.J. Lobl, L.L. Maggiora andj.w. Wilks Purification and analysis of a hepatocyte antiproliferative glyc'opeptide 578 G. Auger, D. Blanot, G.A. Boffa, M.-F. Gournay, J. Van Heijenoort, P. Lambin, P. Maes, C. Nadal and A. Tartar xxx

Structures of human TGFa fragments using two-dimensional proton 581 magnetic resonance spectroscopy and computer simulation K. Han, C.-H. Niu, B.R. Brooks, J. A. Ferretti and P.P. Roller A comparative study of strategy and cleavage and methods by HF and 584 trifluoromethanesulfonic acid: Synthesis ofshope fibroma growth factor and proteoglycan growth factor D.-X. Wang, Y.-Z. Lin. G. Caporaso, P.-Y. Chang, X.-H. Ke and LP. Tarn Substrates of tyrosine-specific protein kinase: Synthetic peptides derived 587 from lipocortins R.G. Yarger, R.H. Berg, S.A. Rotenbergand J.P. Tarn Session X: Neurochemistry Receptor-mediated peptide transport through W.M. Pardridge the blood-brain barrier 593 Neuropeptide co-transmitters in physiologically identified motor neu- 596 rons in Aplysia P.E. Lloyd and D.P. Lotshaw Distinct endogenous ligands for PCP and sigma opioid receptors 601 D.A. DiMaggio, P.C. Contreras andt.l. 0'Donahue Comparison of amyloid from Alzheimer's disease with synthetic peptide 604 L.K. Duffy, D.A. Kirschner, C.L. Joachim, A. Sinclair, H. lnouye and D.J. Selkoe Cyclic CCK-8 analogs highly selective for central receptors 608 B. Charpentier, I. Marseigne, A. Dor, D. Begue, M. Reibaud, J.L. Zundel, J.C. BlanchardandB.P. Roques C. Durieux, D. Pelaprat, Structural requirements for the satiety effect of CCK-8 610 J.D. Rosamond, J.M. Comstock, N.J. Thomas, A.M. Clark, J. C. Blosser, R.D. Simmons, D.L. Gawlak, M.E. Loss, S.J. Augello-Vaisey, A.F. Spatola andd.e. Benovitz A study of the substrate specificity of carboxypeptidase H 613 N.J. Darby, L.D. Fricker, K. Maruthainar and D. G. Smyth xxxi

Relationship between the conformational properties hexapeptides derived from DSLET and DTLET and their opioid selectivity M.-C. Fournie-Zaluski, J. Belleney, G. Gacel, B. Maigret Roques of a new series of 615 delta and B.P. Interaction of the dogfish cyclic tachykinin scyliorhinin II with tachy- 617 kinin NK-1 and NK-2 binding sites J.L. Krstenansky and S.H. Buck Theoretical conformational analysis of ju-selective cyclic opioid peptide 619 analogs B.C. Wilkes and P. W. Schiller Session XI: New biological areas Peptide sequences specified by complementary RNAs represent binding 623 sites for proteins or peptides which interact K.L. Bost and J.E. Blalock Didemnin and its biological properties 626 K.L. Rinehart Identification of two distinct regions of an alternatively spliced site in 632 human plasma fibronectin that promotes cell-type specific adhesion M.J. Humphries, A. Komoriya, S.K. Akiyama, K. Olden and KM. Yamada Melanin-concentrating hormone: Structure-activity studies of a new 635 hormone M.E. Hadley, A.M.L. Castrucci and V.J. Hruby Synthesis and biological activity of peptides inhibiting herpes simplex 638 virus ribonucleotide reductase P. Gaudreau, J. Michaud, S. Rakhit, J.-M. Ferland, J. Gauthier, Y. Langelier and P. Brazeau The synthesis and characterization of 81- and 88-residue peptides: 641 Conserved structures in the protein components of cartilage proteoglycan aggregates P.J. Neame, G.M. Anantharamaiah, J.E. Christner and J.R. Baker Glucagonlike peptide I (7-37) is a potent stimulator of insulin secretion 644 S. Mojsov, G.C. Weir and J.F. Habener xxxn

The design and testing of specific inhibitors of tissue kallikrein: Role 647 of the enzyme in blood pressure regulation J. Burton Detection of new peptaibol antibiotics (mycotoxins) in species and strains 650 of the fungal genus Trichoderma H. Bruckner, C. Kussin and T. Kripp Structure-activity relationships for insect hypertrehalosemic The importance of side chains and termini M.M. Ford, T.K. Hayes andl.l. Keeley hormone: 653 Structure elucidation of the major cytotoxic component of Trididemnum 656 cyanophorum B. Castro, P. Jouin, A. Cave, M. Dufour, B. Banaigs and C. Fransisco Backbone modification of synthetic poly-a-l-amino /. Kohn and R. Longer acids 658 Peptide derivatives specific for a Plasmodium falciparum protease ed in red blood cell invasion by merozoites R. Mayer, I. Picard, F. Bernard, P. Lawton, P. Grellier, J. Schrevel and M. Monsigny involv- 662 Author index 664 Subject index 673 xxxiii