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Book Review Combinatorial Peptide and Nonpeptide Libraries. A Handbook. Edited by G. Jung

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BOOKS
trust, after a visit to the doctor: “should I
really be taking this medication?’ - a
question that is increasingly put to me
(and, no doubt, to other chemists) by
friends or relatives. Instead he presents
background information that is normally
lacking for the reader who has not been
closely involved with science or medicine.
Thus, the book will help to remedy a gap
in understanding that unfortunately exists
for a large part of the educated public (especially in Germany), and which is largely
responsible for the deplorably poor image
of science and technology at present.
Readers of Angewandte Chemie do not, of
course, belong to that tendency. Nevertheless, I recommend them to take a look
at this book by Alfred Burger, and to allow it to circulate among their friends
and relatives, or even to consider it as a
suitable gift. By doing so they would do
their science a good service.
Herbert Waldmann
Institut fur Organische Chemie
der Universitat Karlsruhe
Karlsruhe (Germany)
Ways to Successful Strategies in
Drug Research and Development. By
H. H . Sedlacek, A . M . Sapienza and
I? Eid. VCH Verlagsgesellschaft,
Weinheim, 1996. 250 pp., paperback
DM 128.00.--ISBN
3-527-29415-5.
Critical Success Factors in Biomedical
Research and Pharmaceutical Innovation. By S. W: E Omta. Kluwer,
Dordrecht, 1995. 300 pp., hardcover
$124.50.--ISBN 0-7923-3563-5
Anyone in the pharmaceutical industry
who is or has been involved in challenging
discussions of research and development
strategies, for example in the context of a
major reorganization, will immediately
recognize that the book Ways to Successful Strategies in Drug Research and Development has been written by authors who
have been intimately involved in such exercises. However, rather than formulating
recipes for successful strategies from
specific personal perspectives, the authors
offer a comprehensive outline of important factors, parameters, conditions for
pharmaceutical R & D management, their
interplay and impact on critical R & D
processes, and their assessment in the context of defining overall R & D strategies.
This outline is the result of actual experience with, and recent surveys of, a representative collection of pharmaceutical
companies. Those who have already gone
through such experiences will often have a
sense of “deja vu” on reading about the
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many typical scenarios which the book
describes in a well structured and easily
readable format, shedding its unforgiving
light on both the right and the wrong decisions. For those newly confronted with
these issues, it will be an eye-opener in
many respects. Thus, the book can and
should be recommended to both middle
and upper, junior and senior management
alike. While it covers the many important
internal and external driving forces and
factors which have to be considered in formulating a successful pharmaceutical R &
D strategy, it also reserves ample space to
address important cultural, sociological,
and psychological issues, to discuss important ethical aspects of current and future health care systems, and to review
moral obligations towards humans, animals, and the environment. In some of
these regards, the book reflects the special
expertise of the authors, and appears to
provide a somewhat overly extensive coverage at the cost of other important aspects, such as the impacts, integration,
and management of information and automation technologies, or the assessment,
implementation, and management of research collaborations, joint ventures, or
strategic alliances with academic or industrial groups. However, one can forgive
this bias in view of the many comprehensive and clear representations of current
wisdom, accompanied by expert commentaries and illustrative examples. In this
way the book provides both practical
toolkits and conceptual frameworks for
analyzing the strengths and weaknesses of
one’s own organization and R & D portfolio, for formulating and evaluating different strategic options, and for assessing
their potential risks and benefits.
There are essentially two ways of reading Omta’s book Critical Success Factors
in Biomedical Research and Pharmaceutical Innovation. One would be the hard sequential way of working systematically
through the study methodology, the study
design, theory construction, hypothesis
generation, data collection, processing
and analysis in order to get to the results,
discussions and conclusions. Alternatively, one can start directly with the latter
towards the end of the book, and leave the
more technical part to a later stage in case
of need or particular .interest. In either
case, one quickly learns that this study is
confined to a survey of Dutch universities
and institutes, thus presenting a relatively
narrow perspective. On the industrial side
it is based on a number of (mostly undisclosed) multinational companies, but appears to ignore important companies
from certain geographical areas. However, the conclusions from this statistical
@> VCH Verlag.~ge.~ell.~~hafl
mbH, 0.69451 Weinheim,1997
survey, based on the usual types of crosschecked questionnaires and personal interviews, remain sufficiently vague and so
full of truisms that any concerns about
potential hidden biases become irrelevant.
In fact, anyone concerned with research
management in one way or another may
be surprised to find so much sophisticated
systems theory machinery being used just
to reconfirm what appears to be commonsense or day-to-day experience. However,
the reader interested in learning about
current state-of-the-art systems analysis
instruments may concentrate more on the
first part of the book, which provides an
overview of many techniques, methodologies, theories, concepts, and terminologies, as exemplified in the context of this
specific study. Perhaps more important
than this overview are the occasional discussions of potential weaknesses and pitfalls of such statistical analyses in general,
and the exceptions to statistically based
generalizations that the author points out
in this particular study. The fact that the
data collection was already completed in
the early nineties may be a cause for concern. Since then the world of biomedical
research, particularly that of the pharmaceutical industry, has changed dramatically. Inevitably, therefore, some conclusions of this study have already been
superseded by the rapid pace of development in this area. Finally, a word of caution may be appropriate regarding the
title of the book. It acts as a bait, but with
little meat on the hook. The critical success factors of modern multidisciplinary
biomedical research are not comprehensively addressed here, nor is the definition
and measurement of pharmaceutical innovation discussed at more than a superficial level. Although certainly less attractive, a more conservative title might have
been better, and would be less likely to
leave readers unsatisfied.
Klaus Muller
F. Hoffmann-LaRoche AG
Pharma Research New Technologies
Base1 (Switzerland)
Combinatorial Peptide and Nonpeptide Libraries. A Handbook. Edited by
G. Jung. VCH Verlagsgesellschaft,
Weinheim, 1996. 545 pp., hardcover
3! 135.00.-ISBN 3-527-29380-9
In a few years, combinatorial chemistry
has developed from a largely academic endeavor into a well-respected and much
discussed technique within the pharmaceutical industry. The main reason for the
interest in combinatorial chemistrv is the
possibility of speeding up the drug devel-
0570-0833/97/3604-0416$ 15.00f ,2510
Angew. Chem. Int. Ed. Engl. 1997. 36, No. 4
BOOKS
opment process, mainly by increasing
the number and diversity of compounds
to be tested, thereby increasing the
chances of identifying a compound with
the desired (biological) activity. The field
started out with peptide libraries, but
currently there is a clear shift to nonpeptide libraries, due to the inherent limitations of peptides as therapeutics. This
book, edited by Giinther Jung, is one of
the first to summarize the developments in
this area, with the emphasis on peptide
libraries.
The first three chapters offer an
overview of the possibilities for the synthesis and analysis of libraries. In the first
chapter. Jung goes back to the natural
origins of molecular diversity and libraries, using examples from polypeptide
antibiotics and MHC (major histocompatibility complex) Classes I and 11. In the
final part of Chapter 1, an overview is
given of the remainder of the book, and
references are made to existing reviews in
this field. The emphasis is, as already said,
on all aspects of the design, synthesis,
analysis, and testing of peptide libraries.
Most of the biological applications are
chosen from the MHC and T-cell epitope
field.
Chapter 2 deals with the organic chemistry on the solid phase, with emphasis on
nonpeptide chemistry. The content of this
chapter has been published before as a review paper in Angewandte Chemie. An
overview of existing methods for the synthesis of multiple peptides and peptide libraries is given in Chapter 3. Curiously, a
discussion of the chemistry involved is not
included in this chapter, nor anywhere
else in this book.
In Chapter 4, the portioning-mixing
(split-pool) method is treated extensively
from a theoretical point of view. Chapter
5, by Houghten and coworkers, describes
the use of nonsupport-bound libraries and
details the methods of identifying an active peptide from a combinatorial library.
Angru . C/iem. Inr Ed. Engl. 1997.34. No. 4
In Chapter 6, Lam and Lebl give an
overview of the one-bead-one-compound
concept, with the emphasis on identifying
beads containing an active compound by
coloring. Some examples of nonpeptide libraries are discussed. Peptide and cyclopeptide libraries, synthesized using the
premix method, are dealt with in Chapter
7. Mass-spectrometric analysis of these libraries by electrospray ionization is described in Chapter 8. Another analytical
technique, peptide sequence analysis by
Edman degradation, is the subject of
Chapter 9. This method can be used both
for natural and synthetic peptide mixtures. The application to libraries of
MHC peptides is described. Epitope mapping or identifying and the synthesis of
peptides on pins is the topic of Chapter 10
by Geysen and coworkers, again using
MHC peptides as the example. In Chapter
11, Spatola and Romanovskis again treat
cyclic peptides libraries, although in more
detail, and synthesized in a manner different from that described in Chapter 7. The
use of random peptide libraries in immunology is the topic of Chapter 12, overlapping with Chapter 7. Yet another
method of synthesizing peptides libraries,
the SPOT technique on membrane supports, is described in Chapter 13.
In Chapters 14 and 15 two nonpeptide
libraries are described, first the peptoids
library, as advocated by Chiron, and then
the benzodiazepine library, in an overview
by Ellman. The material presented in
these two chapters has already been published several times elsewhere. The properties of PEG grafted polystyrene tentacle
polymers as a solid phase for organic
chemistry are dealt with in Chapter 16,
followed in Chapter 17 by a general review (including price range) of polymeric
supports for solid phase organic synthesis.
The reverse order of these chapters would
have been more logical. In Chapter 18 the
mass spectrum simulation program
QMass is described. It would have been
C, VCH Verlugsgesellschuff mbH, 0-69451 Weinheim, 1997
more appropriate to include this material
as an appendix to Chapter 8, and to add a
“future prospects” chapter instead. A
glossary and an index form the conclusion
of this book.
As can be expected in such a rapidly
expanding and multifaceted field as combinatorial chemistry, this book is already
outdated to some extent. As remarked
above, the current interest is in nonpeptide libraries. In this respect, the book
may be a disappointment. Despite the
promise of the title, all aspects of the synthesis, analysis, and biological testing of
peptide libraries are discussed in great detail, but only a Iimited amount of space is
devoted to nonpeptide libraries. This is
regrettable, as the techniques used for the
analysis of peptide libraries have only limited applicability to nonpeptides. There is
no information on topics such as diversity
analysis, virtual libraries, library size and
the complexity of mixtures to be tested,
and differences between random and
targeted libraries. These are all “hot” topics in the literature and on the Internet at
the moment, mainly discussed with respect to nonpeptide libraries, although
they have relevance in the peptide field as
well.
In conclusion, this book offers a good
starting point for every chemist who
wants to learn about combinatorial chemistry using peptide libraries. There is a
wealth of practical information about the
synthesis, analysis, and biological testing
of peptide libraries. However, scientists
interested in nonpeptide libraries will
learn little that is new. It is hoped (and
expected) that the next edition, which is
already mentioned in the preface, will fill
the gaps referred to here
Joannes 7: M . Linders,
Harry C. J. Ottenheijm,
Cutherinu J. van Staveren
N. V. Organon
Oss (The Netherlands)
0570-0S33~97~3604-0417$15.00+
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41 7
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