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Essential NMR. By Bernhard Blmich

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Evaluation of Enzyme Inhibitors in
Drug Discovery
By Robert A. Copeland. Wiley-Interscience, Hoboken
2005. 271 pp.,
E 69.90.—ISBN
Modulation of protein function by
interaction with small-molecule inhibitors is central to both chemical biology
(the scientific basis) and the pharmaceutical industry, which turns science
into products of benefit to mankind.
Enzymes are probably the most important class of protein drug targets, owing
to their important roles in life processes
and the fact that enzyme-active sites and
other ligand-binding pockets are ideally
suited for high-affinity interaction with
drugs. Probably every chemist, at least
once during his or her undergraduate
education, learns something about
Michaelis–Menten kinetics, which contains the fundamental equation in enzymology, which describes substrate–
enzyme interaction. But the inhibition
of proteins involves many more aspects
that are less well known and deserve
more attention. Standard biochemistry
textbooks usually fail to teach those subtleties, which anyone dealing with the
interaction between small molecules
and proteins needs to know about. In
his book Evaluation of Enzyme Inhibitors in Drug Discovery, Robert Copeland, whose authority is based on a distinguished career as an enzymologist in
Angew. Chem. Int. Ed. 2005, 44, 6445 – 6446
both industry and academia, provides
an excellent and clearly written work,
which will help many readers to understand this discipline.
In the first two chapters, the author
gives a concise but informative introduction to the fundamental principles of
enzyme catalysis and substrate binding.
Even in these introductory chapters, it
will take the reader only a few paragraphs to appreciate one of the big
strengths of this book: the author generously shares his great experience as an
industrial practitioner, and augments
the theoretical discussion with many
instructive examples in which potential
pitfalls and solutions for frequently
encountered problems are illuminated.
This personal note makes an especially
valuable contribution to the following
chapter, which presents considerations
about assays for the screening of compound libraries.
A major part of this book is dedicated to the reversible modes of inhibitor interactions with enzymes, in which
uncompetitive inhibitors have to be distinguished. The author reminds the
reader that the commonly used IC50
value for the description of inhibitor
efficiency is significantly affected by
the assay conditions, and describes
simple experiments that should be carried out to guarantee a well-designed
assay or to avoid the misinterpretation
of data. Here again, the author achieves
a good balance between an in-depth
kinetic analysis (containing many equations and graphs) and fascinating case
studies of failed or marketed drugs,
which illustrate the theoretical considerations. In the next two chapters, the
mechanistic fundamentals, some practical examples, and the clinical advantages of slow-binding and tight-binding
inhibitors, are discussed thoroughly.
The final chapter discusses irreversible enzyme inactivation and the applications of affinity labels and mechanismbased inactivators as drugs.
As in any book, even this carefully
edited monograph is not free from
errors, but most of these do not distort
the meaning. The index is reasonably
effective for finding particular topics in
the text, but the reader would certainly
have benefited from a list of abbreviations, which is sadly missed when one
makes the effort of working through
the many equations.
In conclusion, Evaluation of Enzyme
Inhibitors in Drug Discovery provides
an excellent introduction to the key
aspects of enzymology, enzyme inhibition, and the development of drugs. It
distinguishes itself from other books by
its balanced discussion of both theory
and experimental practice. In his preface the author modestly describes his
book as a guide for medicinal chemists
and pharmacologists. I think this book
definitely deserves a bigger readership,
and I recommend it to everybody who
is interested in the interaction of proteins with small molecules. Every
chemistry library in academia or industry should own a copy of this book.
Rolf Breinbauer
Max-Planck-Institut f*r
Molekulare Physiologie
and Universit-t Dortmund (Germany)
Essential NMR
By Bernhard Blmich. Springer
Verlag, Heidelberg
2005. 243 pp., softcover E 37.50.—
ISBN 3-540-23605-8
In the 60 years that have passed
since the discovery of the phenomenon
of nuclear magnetic resonance (NMR),
the subject has developed enormously,
partly because of the revolution in
microelectronics and computer technology that has taken place during that
time. In addition to the classical applications in chemical analysis, NMR
spectroscopy has made spectacular
advances into many other areas of application, in medical diagnostics, biomedical research, materials characterization,
process technology, quality assurance,
and even geological research.
The author1s aim was to collect these
different areas of application together
within a single book, in a concise and
informative way, so that scientists and
6 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
technologists can understand the fundamental principles and applications of
NMR spectroscopy. The book consists
of five chapters and an index. The first
two chapters—a brief introduction followed by Chapter 2, “Basic Principles”—are certainly of interest to all
the readers for whom the book is
intended. The topics covered in these
chapters range from the historical development to the necessary equipment, the
physical principles (including the essential mathematics), and the most important measurement techniques. The chapters that follow are more specialized,
and are mainly of interest either to
chemists, physicists, and biologists on
one hand (Chapter 3, “Spectroscopy”),
or to materials scientists and engineers
on the other hand (Chapter 4, “Imaging
and Mass Transport”, and Chapter 5,
“Low-Field and Unilateral NMR”).
However, that division of interests,
which is also suggested by the author,
should not discourage the interested
reader from studying the whole book.
The topics covered in Chapter 3
include the different types of spin–spin
interactions, anisotropy effects, the
basic principles of solid-state NMR
spectroscopy, multidimensional measurement techniques, and studies of
dynamic processes. Chapter 4 begins
with the principles of NMR imaging
and field-gradient techniques, then
describes two- and three-dimensional
imaging techniques and the investigation of mass-transport phenomena.
Unfortunately, the clinical and biomedical imaging techniques, which would
certainly have greatly enhanced the
value of this chapter, are almost completely absent. Lastly, Chapter 5, which
is somewhat shorter, describes methods
for process control and quality assurance, with a particular focus on investigations of polymers.
Someone who takes a look at the
book for the first time, after having
read the above description, will be surprised initially. However, the preface
actually prepares the reader, who
might at first have expected to find a
conventional monograph or textbook,
for a completely different kind of presentation. The material is presented in
the form of figures and pages of text in
a pairwise arrangement. That has led
to the book1s unusually compact A5size oblong format. The figures are of
excellent quality throughout, and the
skillful use of color enables one to
grasp the essential information very
quickly. On the textual pages, the information is presented under headings in
the form of lists of key points. There
are no literature references in Chapters 2–5, apart from the citation of sources for some of the figures.
6 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Altogether, this is a very nice collection, which is certainly suitable as material to accompany a lecture course or a
supplementary study course, and the
author states that he intends it to be
used in that way. One can guess that
the book has, in fact, arisen from such
a collection previously used by the
author. It is not suitable, and is indeed
not intended, as an alternative to a textbook on the subject, or—as would be
more appropriate—separate textbooks
on the different aspects of nuclear magnetic resonance. A very clear and useful
list of such textbooks is provided in the
introductory chapter, although it does
not always refer to the latest editions.
It remains to be seen whether, alongside
those books, this very nicely written and
handsomely produced supplementary
text will achieve the wide readership
among students of the various disciplines that the author and publishers
hope for. It will certainly be bought by
university lecturers, NMR departments,
and libraries.
Arne Ltzen
Institut f*r Reine und Angewandte
Universit-t Oldenburg (Germany)
DOI: 10.1002/anie.200585322
Angew. Chem. Int. Ed. 2005, 44, 6445 – 6446
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