Ciba Foundation Symposium 159 - Catalytic Antibodies

268 Pages·17.574 MB·English

CATALYTIC
ANTIBODIES
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pharmaceutical company of ClBA Limited-now CIBA-GEIGY
Limited. The Foundation operates independently in London under
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Ciba Foundation Svmposium 159
CATALYTIC
ANTIBODIES
A Wiley-lnterscience Publication
1991
JOHN WILEY & SONS
Chichester . New York . Brisbane . Toronto . Singapore
OCiba Foundation 1991
Published in 1991 by John Wiley & Sons Ltd.
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Ciba Foundation Symposia
Ciba Foundation Symposium 159
ix + 259 pages, 66 figures, 10 tables
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available from the British Library
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Contents
Symposium on Catalytic antibodies, held at the Ciba Foundation, London
1-3 October 1990
Editors: Derek J. Chadwick (Organizer) and Joan Marsh
W. Jencks Introduction 1
P.
S. J. Benkovic, J. Adams, K. D. Janda and R. A. Lerner A catalytic
antibody uses a multistep kinetic sequence 4
Discussion 9
I. A. Wilson, R. L. Stanfield, J. M. Rini, J. H. Arevalo,
Schulze-Gahmen, D. H. Fremont and E. A. Stura Structural aspects
U.
of antibodies and antibody-antigen complexes 13
Discussion 28
Y. Arata Nuclear magnetic resonance studies of antibody-antigen
interactions 40
Discussion 50
J. M. Thornton Modelling antibody combining sites: a review 55
Discussion 69
G. R. Nakayama and G. Schultz Approaches to the design of
P.
semisynthetic metal-dependent catalytic antibodies 72
Discussion 8 1
W. Huse Construction of combinatorial antibody expression libraries in
Escherichia coli 91
Discussion 98
A. Pluckthun and 3. Stadlmuller Catalytic antibodies: contributions from
engineering and expression in Escherichia coli 103
Discussion 11 2
V
vi Contents
K. M. Shokat and P. G. Schultz The generation of antibody combining
sites containing catalytic residues 118
Discussion 128
General discussion I 135
L. Sastry, M. Mubaraki, K. D. Janda, S. J. Benkovic and A. Lerner
R.
Screening combinatorial antibody libraries for catalytic acyl transfer
reactions 145
Discussion 151
S. Paul, D. Johnson and R. Massey Binding and multiple hydrolytic
R.
sites in epitopes recognized by catalytic anti-peptide antibodies 156
Discussion 167
D. Hilvert Antibody catalysis of carbon-carbon bond formation 174
Discussion 183
T. Martin, A. Schantz, P. G. Schultz and A. R. Rees
M. R.
Characterization of the mechanism of action of a catalytic
antibody 188
Discussion 197
C. J. Suckling, C. M. Tedford, G. R. Proctor, A. 1. Khalaf, L. M. Bence
and W. H. Stimson Catalytic antibodies: a new window on protein
chemistry 201
Discussion 208
G. M. Blackburn, G. Kingsbury, S. Jayaweera and D. Burton
R.
Expanded transition state analogues 21 1
Discussion 222
B. L. Iverson, S. A. Iverson, K. E. Cameron, G. K. Jahangiri,
D. S. Pasternak and R. A. Lerner Tritylase antibodies 227
Discussion 234
Final general discussion good are catalytic antibodies? 236
How
Potential uses of catalytic antibodies 243
W. P. Jencks Summary 246
Index of contributors 249
Subject index 251
Participants
Arata Faculty of Pharmaceutical Sciences, University of Tokyo,
Y.
Hongo, Bunkyo-ku, Tokyo 113, Japan
S. J. Benkovic Department of Chemistry, College of Science, 152 Davey
Laboratory, The Pennsylvania State University, University Park, PA
16802, USA
G. M. Blackburn Department of Chemistry, University of Sheffield,
Sheffield S3 7HF, UK
K. Brocklehurst Department of Biochemistry, Queen Mary & Westfield
College, Mile End Road, London El 4NS, UK
D. R. Burton Department of Molecular Biology, University of Sheffield,
Sheffield S10 2TN, UK
B. S. Green Department of Pharmaceutical Chemistry, School of
Pharmacy, The Hebrew University of Jerusalem, PO Box 12065,
IL-91120 Jerusalem, Israel
D. E. Hansen Department of Chemistry, Amherst College, Amherst, MA
01002, USA
T. J. R. Harris Glaxo Group Research, 891 Green Road, Greenford,
Middlesex UB6 OHE, UK
D. Hilvert Departments of Molecular Biology & Chemistry, Research
Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla,
CA 92037, USA
W. Huse Ixsys Inc, 3550 General Atomics Court, Suite L103, San Diego,
CA 92121, USA
B. L. Iverson Department of Chemistry, University of Texas at Austin,
Austin, TX 78712, USA
vii
viii Participants
K. D. Janda Departments of Molecular Biology & Chemistry (MB-20),
Research Institute of Scripps Clinic, 10666 North Torrey Pines Road, La
Jolla, CA 92037, USA
W. P. Jencks Graduate Department of Biochemistry, Brandeis University,
Waltham, MA 02254, USA
A. S. Kang Departments of Molecular Biology & Chemistry, Research
Institute of Scripps Clinic, 10666 Torrey Pines Road, La Jolla,
North
CA 92037, USA
R. J. Leatherbarrow Department of Chemistry, Imperial College of
Science, Technology 8c Medicine, London SW7 2AY, UK
R. A. Lerner Departments of Molecular Biology & Chemistry, Research
Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla,
CA 92037, USA
M. T. Martin IGEN Inc, 1530 E Jefferson Street, Rockville, MD 20852,
USA
A. Mountain Department of Protein Engineering, Celltech Ltd, 216 Bath
Road, Slough, Berks SL1 4EN, UK
M. I. Page Department of Chemical & Physical Sciences, Huddersfield
Polytechnic, Queensgate, Huddersfield HD1 3DH, UK
S. Paul Department of Pharmacology, University of Nebraska Medical
Center, 600 South 42nd Street, Omaha, NE 68198-6260, USA
A. Pliickthun Gen-Zentrum der Universitat Munchen, Max-Planck-
Institut fur Biochemie, Am Klopferspitz, D-8033 Martinsried/Munchen,
Germany
P. G. Schultz Department of Chemistry, University of California,
Berkeley, CA 94720, USA
A. W. Schwabacher Department of Chemistry, Iowa State University,
Ames, IA 50011, USA
K. Shokat Department of Chemistry, University of California, Berkeley,
CA 94720, USA
Participants IX
C. J. Suckling Department of Pure & Applied Chemistry, University of
Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow
G1 lLX, UK
C. M. Tedford Department of Pure & Applied Chemistry, University of
Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow
G1 lLX, UK
J. Thornton Department of Biochemistry, University College London,
Gower Street, London WClE 6BT, UK
I. A. Wilson Department of Molecular Biology (MB13), Research
Institute of Scripps Clinic, 10666 North Torrey Pines Road, La Jolla,
CA 92037, USA
Novartis Foundation Symposium
Edited by Derek J. Chadwick, Joan Mash
Copyright 0 1991 by Ciba Foundation
In t roductio n
W. P. Jencks
Graduate Department of Biochemistry, Brandeis University, Waltham, MA 02254-91 10,
USA
This meeting is being held at a very appropriate time on a subject that has
developed rapidly. Many of the people who have participated in this development
are present, and there is no better way to bring a subject of this kind into focus
than to assemble those who have contributed to it.
The question may arise of what I am doing here, since I have never made a
catalytic antibody and have no results to present. The reason is that I wrote a book
some time ago (Catalysis in chemistry and enzymology 1969), because I wanted
a place where I could look things up. In 1968 we had been thinking about
transition states and their stabilization, following, of course, Linus Pauling.
A paragraph in my book points out that since enzymes are complementary to
transition states, it should be possible to prepare antibodies to transition state
analogues that would stabilize transition states and, therefore, catalyse reactions.
If complementarity between the active site and the transition state contributes
significantly to enzymic catalysis, it should be possible to make an enzyme by
constructing such an active site. One way to do this is to prepare an antibody to
a haptenic group which resembles the transition state of a given reaction. The
combining site of the antibody should be complementary to the transition state and
should accelerate the reaction by binding substrates and forcing them to resemble
the transition state. Richard Pincock, who was visiting our department,
attempted to prepare antibodies to transition states of the hydrolysis of an ortho
ester and of a substitution reaction on a sulphonate. The results were entirely
negative, for good reason-we had no monoclonal antibodies and we were looking
at the wrong type of reaction. One needs a reaction that is susceptible to catalysis
and occurs at a reasonable rate in the absence of catalysis. It is also important
to have monoclonal antibodies, because they can be obtained in large quantities.
Raso & Stollar (1975) at Tufts University made antibodies to reduced Schiff
bases of pyridoxal phosphate and tyrosine, and showed that the antibodies
caused a small increase in the rate of transamination of L-tyrosine. This, to
my knowledge, was the first experimental indication that such an advantage
could be conferred by a specific antibody. Major developments in the field came
later, when monoclonal antibodies became available, and were brought about
by the people at this symposium.
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