Table Of ContentPeptides for the New Millennium
Co-Chairsofthe 16thAmerican PeptideSymposium,
Gregg B. Fields (left) and George Barany (right).
Peptides for the New Millennium
Proceedings of the 16th American Peptide Symposium
June 26-July 1, 1999, Minneapolis, Minnesota, U.S.A.
Edited by
Gregg B. Fields
Department of Chemistry and Biochemistry,
Florida Atlantic University,
Boca Raton, Florida, U.S.A.
James P. Tam
Department of Microbiology and Immunology,
Vanderbilt University Medical School,
Nashville, Tennessee, U.S.A.
and
George Barany
Departments ofChemistry and LaboratoryMedicine & Pathology,
University of Minnesota,
Minneapolis, Minnesota, U.S.A.
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Contents
Preface XXXV
16th American PeptideSymposium and American Peptide Society xliii
Symposium Co-Chairs xliii
Symposium Program Committee xliii
Society Officers xliii
Society Councilors xliii
Society Honorary Members xliv
Local Planning Committee xliv
Focus Group Leaders xliv
Local Staff xlv
Local Volunteers xlvi
Symposium Sponsors xlvii
American Peptide Symposia li
The Merrifield Award liii
Vincent du Vigneaud Award lvii
Ralph F. Hirschmann Award in Peptide Chemistry lviii
American Peptide Society Travel Grants lix
The Bruce W. Erickson Young Investigators’ Awards lxi
The ESCOM Awards lxi
Abbreviations lxiii
The 1999 Merrifield Award / Rao Makineni Lecture 1
Mimetic peptides, demanding enzymes, and drug discovery 3
Daniel H. Rich
Young Investigators’ MiniSymposium 17
Bruce W. Erickson: In memoriam 19
Arthur M. Felix
Engineering of a cysteine-containing variant of quadrin, a protein containing the
oligomerization site of the hepatitis delta antigen 20
Matthew J. Saderholm, Paul Saconn, Nimish Shah, and Bruce W. Erickson
vi
Characterization of betabellins 15D and 16D, designedbeta-sandwichproteinsthat
have amyloidogenic properties 22
Amareth Lim, Alexander M. Makhov, Lawreen H. Connors, Jeremy Bond, Hideyo
Inouye, Jack D. Griffith, Daniel A. Kirschner, Catherine E. Costello, and Bruce W.
Erickson
Design and synthesis of inhibitors of botulinum neurotoxin A and B metalloproteases 24
Thorsten K. Oost, Chanokporn Sukonpan, and Daniel H. Rich
Dimerization inhibitors of HIV-1 protease: Effective inhibition requires the
cross-linking of non-identical peptides 26
Michael D. Shultz and Jean A. Chmielewski
Backbonecyclic proteinomimetics derived from the arginine-richdomain of HIV-1
Tat and Rev proteins: One sequence, two conformations, two biological functions 28
Assaf Friedler, Nathan Luedtke, Dorit Friedler, Abraham Loyter, Yitzhak Tor,
and Chaim Gilon
Synthesis of severalO-glycopeptide analogs of enkephalin 30
Scott A. Mitchell, Matthew R. Pratt, Victor J. Hruby, and Robin Polt
Investigating the role of turns in the folding of a predominantly protein 32
Kenneth S. Rotondi, Kannan Gunasekaran, and Lila M. Gierasch
Receptor-bound conformations of integrin antagonists by NMR
spectroscopy 34
Elsa Locardi, Ralph-Heiko Mattern, Timothy I. Malaney, Daniel G. Mullen,
Robert Minasyan, Michael D. Pierschbacher, and Murray Goodman
Design,synthesis, and characterization of two core modules of bovine pancreatic
trypsin inhibitor 36
Natalia Carulla, Clare Woodward, and George Barany
The fine tuning of high affinity and selective non-peptide agonists of the
receptor via solution and solid-phase 38
Josue Alfaro-Lopez, Toru Okayama, Keiko Hosohata, Peg Davis, Frank Porreca,
Henry I. Yamamura, and Victor J. Hruby
Cyclic dodecapeptides form ion channels in lipid bilayers 40
Dongxia Wang, Lili Guo, Patrick J. Edwards, Larry R. Jones, and
Roger W. Roeske
Synthesis and evaluation of potential affinity labels for opioid receptors 42
Heekyung Choi, Thomas F. Murray, and Jane V. Aldrich
Synthetic Methodologies (including Large-Scale Synthesis) 45
Polyethyleneglycol-based chains of precise length for chemobodies 47
Keith Rose and Jean Vizzavona
vii
(Nsc) as an amino-protecting group
and its application for peptide synthesis 50
Hack-Joo Kim and Vladmir V. Samukov
Nsc- and Fmoc-amino acids for automated solid-phase peptide synthesis: Comparative
study of the stability in various conditions 53
Yeon Sun Lee, Hyun Jin Lee, Doyoung Lee, and Hack-Joo Kim
In situ generation of Fmoc amino acid chlorides for extremely difficultcouplings to
stericallyhindered secondary amines in solid-phase peptidesynthesis 55
Eliezer Falb, Tamar Yechezkel, Yosphe Salitra, Gary Gellerman, Dan Muller,
and Chaim Gilon
Evaluation of ivDde as a quasi-orthogonal protecting group for Fmocsolid-phase
peptide synthesis 58
R. Randy Wilhelm, Ananth Srinivasan, and Michelle A. Schmidt
(Nbs): A new protective group for the indole moiety of
tryptophan 60
Aydar N. Sabirov, Vladimir V. Samukov, Pavel I. Pozdnyakov, and Hack-Joo Kim
Practical asymmetric synthesis of glutamic acids 62
Vadim A. Soloshonok, Chaozhong Cai, and Victor J. Hruby
Formation of substituted aromatic rings in amino acid systems via ruthenium activated
reactions 64
Chris W. West, Jim W. Janetka, and Daniel H. Rich
O-Acetyl-L-homoserine: A versatile synthon for the synthesis of L-homoserine
peptides and 3-amino-2-pyrrolidinones 66
Guenter Knaup, Karlheinz Drauz, and Michael Schwarm
Asymmetric synthesis of free unusual acid esters via
C-C bond formation and simultaneous deprotection/purification 68
Guigen Li, Sun Hee Kim, Han-Xun Wei, Jason D. Hook, and Keith A. Fitzgerald
High yield synthesis of heterocyclic alaninederivatives 70
Paula M.T. Ferreira, Hernâni LS. Maia, and Luís S. Monteiro
Synthesis of(2S,4R) 4-aminoethyl-L-Pro and (2S,4R)-4-carboxymethyl-L-Pro from
(2S,4R)- ester 72
Dewey G. McCafferty, Stephen L. Schneider, and Bruce W. Erickson
A highly effective method for synthesis of arginines 74
Sotir Zakhariev, Zoltán Székely, Corrado Guarnaccia, Nikolinka Antcheva,
and Sándor Pongor
Diffusion phenomena and reactivity using polymer supports: A principal
investigation 76
Wolfgang E. Rapp
viii
Solid-phase peptide synthesis in the direction 78
Nathalie Thieriet, Jordi Alsina, Francois Guibé, and Fernando Albericio
Diisopropylethylamine salts for protectedamino acids: Direct synthesis of
peptides on solid-phase 80
Preeti Balse, Guoxia Han, Victor J. Hruby, and Lele Sun
Synthesis of phosphorylated CRE BP1(19-106) amide using a phosphopeptide
thioester prepared directly by an Fmoc solid-phase method 82
Saburo Aimoto, Koki Hasegawa, Xiangqun Li, and Toru Kawakami
Preparation of phosphohistidyl peptides via oxidative coupling of H-phosphonates 84
Bennet J. Harding, W. Scott Dodson, Brian D. Bennett, William S. Marshall,
and Mark A. Jarosinski
Preparation and incorporation into small peptides and combinatorial libraries of
phosphohistidine analogs for study of prokaryotic two-component signal
transduction systems 86
Michael C. Pirrung, Sandra J. Drabik, Kurt V. Gothelf, Kenneth D. James,
and Tao Pei
Synthesis of phosphonamides and thiophosphonamides by a one-pot
activation-coupling-oxidation protocol 89
Sheila D. Rushing and Robert P. Hammer
Synthesis of phosphonopeptide and thiophosphonopeptide analogs as inhibitors of
carboxypeptidase A 91
Hong Fan, Yuhong Zhao, Larry Byers, and Robert P. Hammer
Application of solid-phase Ellman's reagent for preparation of disulfide-paired
isomers of SI 94
Balazs Hargittai, Ioana Annis, and George Barany
Alternative solid-phase reagents for formation of intramolecular sulfur-sulfur
bridges in peptides under mild conditions 96
Ioana Annis and George Barany
An evaluation of a novel safety catch linker for development of cyclic peptide
libraries 98
G.T. Bourne, R.P. McGeary, S.W. Golding, W.D.F. Meutermans,
P.F. Alewood, and M.L. Smythe
Solid-phase synthesis of peptide aldehydes by a Backbone Amide Linker (BAL)
strategy 100
Fanny Guillaumie, Nicholas M. Kelly, Joseph C. Kappel, George Barany,
and Knud J. Jensen
Backbone Amide Linker (BAL) methodology to accommodateC-terminal hindered,
unreactive, and/or sensitive modifications 102
Jordi Alsina, T. Scott Yokum, Fernando Albericio, and George Barany
ix
A new tartaric acid-based linker for the synthesis of C-terminalpeptide
104
Jean-Sébastien Fruchart, Cyrille Grandjean, Dominique Bonnet, Corinne
Rommens, Hélène Gras-Masse, and Oleg Melnyk
A new approach to the guanidinylation of peptides and peptidomimetics including
aminoglycosides and related drugs 107
Tracy J. Baker and Murray Goodman
Photoaffinity-labeled probes for the study of isoprenoid recognition sites 109
Tamara A. Kale and Mark D. Distefano
Orthogonal methods for the synthesis of multiplylabeled peptide probes
and substrates 111
Michael F. Songster, Sara Biancalana, Ronald M. Cook, Daren J. Dick,
and Derek Hudson
Strategies for the synthesis of labeled peptides 113
Lisa Bibbs, Nicholas P. Ambulos, Steven A. Kates, Ashok Khatri, Katalin F.
Medzihradszky, George Ösapay, and Susan T. Weintraub
Orthogonal segment ligation 115
Zhenwei Miao, Qitao Yu, Yi-An Lu, Jin-Long Yang, Kalle Kaljuste,
Chengwei Wu, Li Huang, and James P. Tam
Use of orthogonal ligation methods for the synthesis of hetero peptide dendrimer 118
Chuan-Fa Liu, Chang Rao, and James P. Tam
Minimization of side reactions during removal of the formyl protecting group
from the group of lysine 120
Paul D. Semchuk, Marc Genest, Leslie H. Kondejewski, and Robert S. Hodges
Mechanistic studies of an unusual amide bond scission 122
Christopher J. Creighton, Todd T. Romoff, Jane H. Bu, and Murray Goodman
Novel methods of making (amidated)peptides: Rapid gram quantities as intein
fusions and ton quantities from fusion proteins in the milk of transgenic animals 124
Ian R. Cottingham, Alan Millar, and Colin McKee
Process research toward scale-up and industrial preparation of
RPR109891 126
James J. Mencel, Benoit J. Vanasse, Richard G. Woodward, James P. Sherbine,
Robert C. Liu, Diane C. Salazar, Harshavadan C. Shah, Matthew R. Powers,
Adam W. Sledeski, Gregory C. Kubiak, David S. Teager, Neville L. Holder,
Walter Rodriguez, Simon F. Golec, William L. Studt, Philippe Pitchen, Witold L.
Tomasik, Vincent L. Windisch, Michael D. Thompson, Anthony T. Gardetto,
Geoffrey A. D'Netto, and David J. Taube
Synthesis of cyclic hexapeptide core of antifungal drug candidates 129
Vimal Kishore, Derek Wodka, Edwin O. Lundell, Kenneth W. Funk, Leping Li,
and Larry L. Klein
x
Largescale synthesis of a 27-mer: Identification, characterization and suppression
of a diastereomer contaminant 131
Stephen P. Powers, Kathleen M. Keating, Jo-Ann Jablonski, Henry M. Franzén,
and John Richards
The chemical synthesis of agouti-related protein form C 133
Charles C. Jimenez, J. Mark Quillan, Edward T. Wei, Wolfgang Sadee, and
Jaw-Kang Chang
Chemical synthesis and characterization of the hypothalamic form of CART:
CART(69-116), a new anorectic neuropeptide 136
W. Scott Dodson, Douglas M. Lenz, Bennet J. Harding, Thomas J. Zamborelli,
Mitsuru Haniu, Yunjen Young, and Mark A. Jarosinski
Application of hydrated salt as a source of essential water for enzymatic peptide
synthesis in organic media 138
Gui-ling Tian, Yuan-yuan Hua, Guo-wen Xing, Xiao-fei He, and Yun-hua Ye
Enzymatic synthesis of N-protected amino acid-steroid derivativesin organic solvent 140
Yun-hua Ye, Guo-wen Xing, Ai-xin Yan, Gui-ling Tian, and Chong-xi Li
Peptide amidase-catalyzed C-terminalpeptideamidation in a mixture of
organic solvents 142
Václav Cerovsky and Maria-Regina Kula
Extending the utility of subtilisin-catalyzed peptidesynthesis in organic solvents 144
Irina V. Getun, Irina Yu. Filippova, Elena N. Lysogorskaya, Anna V. Bacheva,
and Elena S. Oksenoit
Backbone amide protection in solid-phase synthesis of peptide isosteres derived
from N-terminal 146
Thomas Groth, Morten Meldal, and Klaus Bock
An efficient preparation of O-succinimidyl carbamate derivatives from N-protected
acids: Application to the synthesis of urea containing pseudopeptides
and oligoureas 148
Gilles Guichard, Vincent Semetey, Claude Didierjean, André Aubry, Marc
Rodriguez, and Jean-Paul Briand
Mimicry of peptide backbone and side-chain functions: Synthesis of 5- and 7-
hydroxymethyl indolizidinone amino acids and indolizidinone amino
dicarboxylate, constrained Ser-Pro and Glu-Prosurrogates 150
Felix Polyak and William D. Lubell
A flexible regioselective method for bicyclization of peptides 153
Petra Johannesson, Gunnar Lindeberg, Weimin Tong, Adolf Gogoll,
Anders Karlén, and Anders Hallberg
Stereoselectivesynthesis of dipeptidomimetics using chiral allylic aziridines 155
Erika Larsson, Wei Berts, and Kristina Luthman
