1/2001
ChemBioChem is a European journal of chemical biology;
it is owned by a group of European scientific societies and
published by WILEY-VCH. Contributions in ChemBioChem cover chemical biology and biological
chemistry, medicinal chemistry, bioinorganic and bioorganic chemistry, biochemistry, molecular
and structural biology, i.e. research of the overlapping areas between chemistry and biology.
ChemBioChem publishes Short Communications and Full Papers as well as Reviews, Minireviews,
Highlights, Concepts, and Book Reviews.
http://www.chembiochem.com
http://www.interscience.wiley.com
D
Chemistry
meets
Biology
uring the last few decades hardly any discipline of the natural sciences has
undergone such a breathtaking transformation as biology. From a science with a
strongly descriptive and phenomenological character, biology was transformed
into a molecular science within a very short period of time. The explosion of
research in structural biology, which describes biological processes in molecular
detail, has made it very clear that biological processes can be traced back to
chemical reactions and that they depend on the structure and interactions of
molecules. Thus, biology is chemical by its very nature. In the past, this insight led
to the development of biochemistry, molecular biology and modern pharmacology. Today it is spurring an increasing demand for structural chemical thinking
and research activities at the interface between chemistry and biology in the life
sciences. This interfacial discipline, commonly referred to as ªBioorganic
Chemistryº, is currently changing its face.
The widespread definition of bioorganic chemistry in mechanistic terms, which
The merging of chemical
and biological expertise
is paramount to
success
CHEMBIOCHEM 2001, 2, No. 1
originated from the first generation of research activities in the field, is now
complemented by various new approaches. Increasingly, organic chemists are
expanding the chemical toolbox for structural and functional investigation of
biological phenomena in molecular detail, thereby facilitating our understanding
of biological processes. The focus of these enterprises is to create chemical tools
that can be used as molecular flashlights to shed light on cellular processes that
cannot be fully studied with the existing methodologies of structural biology, cell
biology and biochemistry. This change in focus is also reflected by a change in
the name of the field, which is increasingly characterised as ªChemical Biologyº.
In these interdisciplinary research projects, the merging of chemical and
biological expertise is paramount to success. Here, bioorganic chemists/chemical
biologists carry out research in both synthetic organic chemistry and biology,
either in one laboratory with expertise in both disciplines or by close
WILEY-VCH-Verlag GmbH, D-69451 Weinheim, 2001
1439-4227/01/02/01 $ 17.50+.50/0
3
An end to the somewhat
artificial division
of chemistry and
biology into two
sciences
collaboration between chemistry and biology labs. This development calls for an
end to the somewhat artificial division of chemistry and biology into two sciences
with only sparse connections. It seems to us, however, that today's reality in
many bioorganic chemistry laboratories is somewhat different and that many
organic chemists, who may characterise themselves as bioorganic chemists or
chemical biologists, continue to follow traditional tracks based solely on organic
chemistry. In our opinion this tendency raises problems both in terms of research,
as it slows the development of a highly dynamic field, and in terms of chemical
education, as we believe that chemists should strengthen their advanced training
in biology and biologists need a strong grounding in chemistry.
The spectacular advances achieved by organic synthesis during recent decades,
for instance in the synthesis of natural products, highlight the fact that the
methodology of modern organic synthesis is, in principle, able to generate
almost any nonpolymeric biologically active natural compound. In this sense
organic chemistry has reached a high level of efficiency. However, it remains true
that the most complex natural products can only be synthesised in a reasonable
time and with reasonable yield and effort by the most potent research groups. In
addition, numerous fundamental problems remain unsolved; for example,
selective CÿH activation and asymmetric catalysis require intensive further
development. Many syntheses remain long and cumbersome, a problem which
could, for instance, be alleviated by efficient domino processes. As a consequence, the methodology of organic synthesis and the art of total synthesis need
to be developed further. We believe, however, that the focus of this development
should differ fundamentally from the approach taken during the last few
decades. We have witnessed impressive achievements of total synthesis, which
were often executed during intense competition culminating in races to reach
ªmolecular summitsº and to meet the challenge of building molecules ªjust
because they are thereº. (For a discussion of the potential tensions surrounding
this issue, see: R. F. Service, Science 1999, 285, 184 ± 187.)
Highly interdisciplinary research fields in which
biology and chemistry are strongly
interconnected
I
n light of the demand and the wealth of problems posed for organic synthesis
by the modern life sciences, the goal of synthetic endeavours should be to focus
on properties rather than complexity. For example, the guidelines for the
planning and execution of a research project for a bioorganic chemist/chemical
biologist should originate from a biological problem, and a number of important
questions, such as ªWhich biological system would I like to study? Where are the
most interesting open questions and how can I address them by employing
synthetic organic chemistry as the key technique?º, should be asked
before venturing on a synthetic endeavour. The same holds for methodology. Approaching a biological problem from this direction and the
subsequent application of novel synthetic compounds to biological problems
will undoubtedly create opportunities and yield insights that are presently
inaccessible using only established biological methods. Still, many biologists are
unaware that approaches based on organic chemistry can be of enormous help
here.
Since organic chemists are well trained in structural thinking and in analysing
problems based on chemical structures, an appropriate starting point for them to
begin research at the interface between organic chemistry and biology may be to
approach the biological phenomenon from this direction.
4
WILEY-VCH-Verlag GmbH, D-69451 Weinheim, 2001
1439-4227/01/02/01 $ 17.50+.50/0
CHEMBIOCHEM 2001, 2, No. 1
However, carrying out such interdisciplinary investigations poses hurdles and
Chemists and biologists
need to become more
open-minded ...
towards the different ªculturesº of
their respective
disciplines
barriers for both biologists and chemists that are, to a major extent, a result of
their different training. The average biologist is usually not as well trained in
structural thinking and analysis as the average chemist. Thus, biologists will often
not be able to identify prevailing chemical problems, and the astonishing
question ªHow long will it take you to make that molecule?º is a frequent
demoralising experience for chemists engaged in joint research projects. On the
other hand, with the current education in chemistry it may be difficult for a
chemist to judge where the most important demands and opportunities for new
methods for the life sciences are. For example, it would be a significant
improvement, currently addressed only by very few chemists, if complex,
biologically active natural products could be synthesised reliably in an
automated fashion. Still, many chemists hold the opinion that this is generally
impractical. We agree that this is true in many cases and are aware that ªchemical
intuitionº is often crucial to success. However, being able to carry out certain
organic syntheses in a programmed, automated fashion would not only
dramatically increase the diversity of organic molecules, it would also have an
immediate impact on combinatorial chemistry, structural biology, functional
genomics and proteomics.
Combinatorial chemistry, high-throughput screening, evolutive biotechnology,
single molecule detection, chip technology and nanotechnology, being highly
interdisciplinary research fields in which biology and chemistry are strongly
interconnected, will further prosper from contributions by researchers from both
fields who are aware of each others' demands. Here, bioorganic chemistry can
provide methodologies that allow, for example, the rapid identification of
inhibitors for different protein domains, sub-domains, catalytic centres or
posttranslational modifications on the same protein. This enables the direct
investigation of functional protein epitopes on the molecular level and adds up
to common genetics approaches such as gene knock-out or overexpression
strategies. Chemists need to address these issues in a strategically focused
manner based on a solid cell-biology background.
Close cooperation between
well-trained scientists
A stimulating intellectual atmosphere
W
hat does this require? As mentioned above, in terms of education chemists
need to complement their training in chemistry with training courses in such
topics as cell biology, genetics, practical molecular biology and biochemistry.
Biologists, in turn, would profit by strengthening their competence in chemistry
and by getting involved in the chemists' culture of ªthinking in structuresº. In
terms of research and joint interdisciplinary projects, chemists and biologists
both need to become more open-minded towards each others' approaches and
to accept and understand the different ªculturesº of their respective disciplines.
The result would be a trustful, truly interdisciplinary collaboration in which
chemists and biologists benefit from their respective strengths and in which one
partner does not view the other simply as a source of chemicals or as a source of
assaying and motivation.
S
uch interdisciplinary research enterprises may, in practice, most efficiently be
carried out in research centres housing both ªbioorganic chemistsº and ªchemical
biologistsº. If both chemical and biological expertise can be established within a
single research group of sufficient size, interdisciplinary work will certainly
flourish most readily. However, chemistry and biology demand such a wide
CHEMBIOCHEM 2001, 2, No. 1
WILEY-VCH-Verlag GmbH, D-69451 Weinheim, 2001
1439-4227/01/02/01 $ 17.50+.50/0
5
ChemBioChem ... will
conquer a firm and
important position
in the landscape of
scientific publishing
variety of different techniques that, in our point of view, close cooperation
between well-trained scientists, each being expert in their own discipline, may
prove to be much more efficient and realistic. Nevertheless, this requires
awareness and at least a sound knowledge of each others' disciplines. Many
universities, research organisations and some funding agencies have recognised
the opportunities that have opened up in this disciplinary interface and are
beginning to take steps to establish such research centres or to encourage
interdisciplinary collaborations. Thus, numerous academic openings and professorships are becoming available in the field of bioorganic chemistry/chemical
biology; however, at least in Europe, chemists with interdisciplinary training (in
the sense of the argumentation term described here) appear to be in short
supply. Thus, in addition to establishing such interdisciplinary research centres,
there is a need for training opportunities that not only link chemistry and biology,
but also, for example, biology and informatics, or biochemistry/chemistry and
bio- or nanotechnology.
Research centres which focus on combining interdisciplinary research and
Herbert Waldmann
(Editorial Advisory
Board Member)
technology would seed a stimulating intellectual atmosphere. At the same time,
many more laboratories focused on bioorganic chemistry (in the sense of being
competent in both biology and organic chemistry) need to be established in
academia all over Europe. Students and researchers not only need a sense for
pharmacological or diagnostic applications of combinatorial techniques, but also
for other fields of technology, such as supramolecular chemistry, nanotechnology, computer sciences (bio-informatics) and sensors. To be sound for future
development, it would be important that laboratories directed by young
independent scientists were established in such centres. At the same time, the
foundation of technological start-up companies should be supported to add up
to this stimulating atmosphere and to provide future perspectives for the
personnel trained. We do not mean to suggest that research with strong
potential for economic application should be preferentially funded. But basic
research may be transformed into ªapplicationsº or ªproductsº faster in such an
environment.
F
Michael Famulok
(Editorial Advisory
Board Member)
inally, the chemical literature will more and more have to respond to this
rapidly occurring change in focus. Journals like ChemBioChem will be in
increasing demand. Undoubtedly they will conquer a firm and important
position in the landscape of scientific publishing. The first issues of ChemBioChem
have already demonstrated that the scientific community is very responsive to
this offer and the journal is likely to grow into one of the premier publishing
bodies for ªChemical Biologyº and ªBioorganic Chemistryº in the years to come.
Prof. Dr. Herbert Waldmann
Max-Planck-Institut für Molekulare Physiologie
and Universität Dortmund, Fb. 3, Organische Chemie
Otto-Hahn-Strasse 11, 44227 Dortmund (Germany)
Fax: (‡ 49) 231-133-2499
E-mail: [email protected]
6
WILEY-VCH-Verlag GmbH, D-69451 Weinheim, 2001
Prof. Dr. Michael Famulok
KekuleÂ-Institut für Organische Chemie und Biochemie
Universität Bonn
Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
Fax: (‡ 49) 228-735-388
E-mail: [email protected]
1439-4227/01/02/01 $ 17.50+.50/0
CHEMBIOCHEM 2001, 2, No. 1