Recent Trends in Molecular Recognition

254 Pages·1998·8.041 MB·English

by  B. M. Trost (auth.), F. Diederich, H. Künzer (eds.)

Ernst Schering Research Foundation Workshop 26
Recent Trends in Molecular Recognition
Springer-Verlag Berlin Heidelberg GmbH
Ernst Schering Research Foundation
Workshop 26
Recent Trends
in Molecular Recognition
F. Diederich, H. KOnzer
Editors
With 99 Figures and 8 Tables
i
Springer
Series Editors: G. Stock and U.-F. Habenicht
ISSN 0947-6075
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lSSN 0947-6075
26. Recent trends in molecular recognition. - 1998
Recent trends in molecular recognition: with 8 tables / F. Diederich; H. Kiinzer ed. -
Berlin; Heidelberg; New York; Barcelona; Hong Kong; London; Milan; Paris; Singa-
pore; Tokyo: Springer, 1998
(Ernst Schering Research Foundation Workshop; 26)
ISBN 978-3-662-03576-4 ISBN 978-3-662-03574-0 (eBook)
DOI 10.1007/ 978-3-662-03574-0
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Preface
Reasoning in terms of molecular recognition may be traced back to
Emil Fischer, who practiced the art of chemistry at Humboldt Univer-
sity in Prussian Berlin a century ago. He was a man of seminal vision
when he postulated in 1894 that enzymes recognize their substrates ac-
cording to the lock-and-key principle. I am quite convinced that he was
fully aware of the future impact of this principle, which he enunciated
far ahead of its time. It was actually ignored for almost 30 years before
being rediscovered by others and given its rightfully important stature
and influence. My conviction is based on the unique instinct of Fischer
in many other matters; remember that he correctly predicted the abso-
lute configuration of D-glyceraldehyde and thus of the carbohydrates
50 years before the Bijvoet X-ray structure of the sodium-rubidium salt
of (+ )-tartaric acid was elucidated.
Today, it is clearly recognized that molecular recognition impacts
and determines all life processes. It has become a key research field in
both chemistry and biology and the emerging interface of what now is
being called "chemical biology."
When browsing through the December 1997 issue of Angew.
Chern., for example, 22 out of 43 contributions could be classified as
dealing with various aspects of supramolecular chemistry and molecu-
lar recognition. This is representative for all major journals such as
Chern. Cornrnun., Angew. Chern., 1. Arn. Chern. Soc., and, when includ-
ing biomolecular recognition, it is to a large extent also true for Nature
and Science.
Molecular recognition research pursues the atomistic understanding
of individual intermolecular interactions in molecular complexes and
VI Preface
The Participants of the workshop
large assemblies of chemical or biological small macromolecules. The
technological advances derived from this knowledge are particularly
important, diverse, and directly evident in the pharmaceutical industry
in areas such as:
- Rational, X-ray, or NMR structure-based drug design and lead opti-
mization.
- Identification through genomics, of well-defined enzymes and re-
ceptors as future targets for drug discovery. It will be increasingly
relevant, given the extremely large number of possible targets
opened up by genomics (e.g., more than 1500 protein kinases alone)
to rapidly identify "well-behaved" future targets, such as those that
bind their substrates in strongly concave/convex relationships and
not based on large protein surface interactions.
- Antisense technology and DNA binding and cleavage towards con-
trolling gene expression are ambitious yet equally important targets
in the pharmaceutical and biotech industry as is increasingly the
search for rational interfering though small molecules with protein-
saccharide recognition.
Preface VII
- Biological transport and bioavailability are important processes that
depend on intermolecular interactions and the partitioning of small
molecules between various biotissues and require enhanced molecu-
lar understanding.
- Bulk chemical production will need more efficient, economic and
ecologically balanced synthetic methods. Basically all chemical
conversions should be made catalytic and, if needed, stereoselec-
tive. The development of stereoselective synthesis and asymmetric
catalysis increasingly sees principles of molecular recognition ap-
plied to the design of more efficient reagents, catalysts, and tem-
plates.
Under the auspices of the Ernst Schering Research Foundation, a 2-day
workshop held in Berlin in February 1998 entitled "Recent Trends in
Molecular Recognition" addressed novel basic developments of poten-
tial relevance to drug research efforts in the pharmaceutical industry.
Eleven lectures delivered during this event by a multidisciplinary inter-
national panel of renowned scholars are documented in this volume.
Although a workshop of this size cannot touch upon all the facets of
the subject, readers of this monograph will find a balanced coverage of
timely research topics in molecular recognition.
F. Diederich
H. Kiinzer
Table of Contents
Designing Transition Metal Complexes
for Molecular Recognition in Synthetic Transformations
B.M. Trost . ....................... .
2 REDOR NMR of Biological Solids:
From Protein Binding Sites to Bacterial Cell Walls
1. Schaefer ..................... 25
3 Molecular and Dendritic Receptors for Small Biomolecules
F. Diederich ..................... 53
4 Molecular Recognition of DNA by Ecteinascidin 743
B.M. Moore II, F.e. Seaman, and L.H. Hurley 81
5 New Tools for Drug Design
Based on Protein Ligand Recognition Principles
G. Klebe . ............... . 97
6 Sequence-Specific Recognition of DNA
and Control of Gene Expression
by Oligonucleotide-Intercalator Conjugates
e. e.
Helene, Giovannangeli, i.-S. Sun, and T. Garestier .. 119
7 Combinatorial Nucleic Acid Libraries:
The New World of Aptamers and Ribozymes
M. Famulok . . . . . . . . . . . . . . . . . . . . . . . . . . 135
X Table of Contents
8 Sequence Specific Recognition of Double Stranded DNA
by Peptide Nucleic Acid
P.E. Nielsen . . . . . . . . . . . . . . . . . . . . . . . . . . 151
9 Solid Phase Libraries of Glycopeptide Templates in the Study
of Complex Oligosaccharide-Receptor Interactions
M. Meldal, P.M. StHilaire, and K. Bock ........... 169
10 The Molecular Recognition of Saccharides
and Glycoprotein-Inspired Materials
L.L. Kiessling . . . . . . . . . . . . . . . . . . . . . . 183
11 Self-Organized Autocatalytic Chemical Networks
and Molecular Ecosystems:
Do They Provide the Experimental Tools for Modeling
the Transition from Inanimate to Animate Chemistry?
M.R. Ghadiri ...................... 213
Subject Index ......................................... 239
Previous Volumes Published in this Series .................. 245