Book reviews

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Pharmaceutical Chemistry

Christine M. Bladon, Wiley, UK, 2002, xii + 221 pp., price £24.95, ISBN 0-471-49637-5 Search PubMedThe continuing increase in the teaching of medicinal and pharmaceutical chemistry, either as part of a chemistry degree or as a separate course, has resulted in the publication of a number of medicinal chemistry textbooks of variable quality. Perhaps understandably, these books have usually centred on ‘small molecules’, which currently comprise the majority of marketed drugs. However, recent innovations in synthetic chemistry and molecular biology have resulted in the emergence of biomacromolecules as drugs, and it is these higher molecular weight compounds that form the subject of this book.

The book is derived from a series of final-year undergraduate lectures presented by the author, and comprises an introductory chapter, followed by five subject chapters. These cover endogenous peptides and proteins and their modification, therapeutic aspects of the immune system, oligonucleotides in gene- and antisense-therapy, and oligosaccharides. A concise overview of the medicinal chemistry and molecular biology associated with each class of biomacromolecule is given, and several contemporary examples of drugs are provided. The inclusion of examples of monoclonal antibodies and antibody-toxin conjugates for the treatment of cancer, and of antisense molecules as antitumour and antiviral agents, is particularly timely. Although a number of related approaches, including antibody-directed enzyme prodrug therapy (ADEPT) for cancer, are not mentioned, overall the book provides an excellent introduction to biomacromolecules as therapeutic agents. Each chapter concludes with an extensive list of further reading and research publications, and a useful appendix and glossary provide a summary of the basic biochemistry and terminology relating to each class of biomacromolecule.

Medicinal and pharmaceutical chemistry students will certainly find this book informative and good value, as will those studying related subjects at the chemistry–biology interface. However, a basic understanding of biochemistry and molecular biology is required, and the book may be more appropriate reading material for postgraduate-level degree courses. This book will also be of wider interest to chemists who wish to gain a better understanding of molecular biology and pharmaceutical biotechnology.

Roger J. Griffin
Northern Institute for Cancer Research,University of Newcastle upon Tyne, UK

Tetrahedron Organic Chemistry Series Volume 21 Biodiversity and Natural Product Diversity

Francesco Pietra, Pergamon Press, Oxford, UK, 2002, price USD 45, xiv + 351 pp. ISBN 0-08-043707-9/0 Search PubMedThis is a very wide-ranging book, which almost makes it impossible to give adequate coverage to its intended remit. It was designed “to provide an all-encompassing vision of diversity of natural products in the perspective of biodiversity”. Whilst acknowledging that the expansive remit of this book may limit the extent of coverage, I have already found it extremely useful to defend natural product chemistry in grant applications. The intended audience of the book is almost certainly those involved in natural product chemistry, whether in academia, or industry, as a very high degree of familiarity with the material is assumed.

The first two parts of the book set the stage for the remainder by defining biodiversity, the relationship between this and natural product diversity. By attempting to do this in only a few pages, it makes a very good summary of these issues, but some important detail has been omitted. Beginners in natural product chemistry will find this section useful to introduce concepts and issues of current concern in this research area. This is the section that could most benefit from being expanded.

The next sections of the book concentrate on comparing natural product diversity at ecosystem level and at functional level. Terrestrial and freshwater biomes are defined and the structural diversity in each is investigated through the use of representative examples. These are generally well chosen, although I found the omission of the microcystins, and other products of cyanobacteria to be most peculiar. The use of a structural complexity index and size metric are useful to give an at-a-glance feeling for the skeletal complexity of natural products, although the concept appears to have been applied differently from the original definition, leading to erroneous values. The different ecological zones in the oceans are discussed next in the light of natural product diversity. The next chapter discusses the issue of finding natural products in common between different taxa. What is particularly interesting here is the sheer number of metabolites found in common between marine and terrestrial species.

Chapter 9 compares the diversity of natural products derived from terrestrial environments to those found in marine species. The tabulated data clearly indicate that Pietra's favourite source of natural products, the oceans, provide the greater complexity. A brief chapter on life in extreme environments is followed by a graphic analysis of skeletal diversity and complexity in natural products. The graphics here do not aid a clear understanding of the comparisons made in the text. In future editions of this text a better way of representing this information needs to be found.

The next part of the book discusses natural product diversity at the functional level. One chapter covers the known ecological functions of secondary metabolites followed by a chapter on the applications of natural products for pharmaceutical applications. This chapter is one of the most useful in the book as it allows the reader to determine the status of compounds in current trials, although, given the nature of this information, some of it is already out of date.

After this the role of biotechnology and chemical synthesis is discussed with a focus on the formation of un-natural products by combinatorial biosynthesis and the solving of the supply problem which blights the full exploitation of many complex natural products. The chapter on synthesis is a treasure-trove of ground-breaking natural products syntheses, useful for both teaching and research. Also included are examples of synthetic pharmaceuticals inspired by natural products. The final section is concerned with the loss of biodiversity and its impact on natural product diversity. Possible solutions are provided in the last chapter which provides possible means to manage natural product diversity.

What I found most unusual for this kind of text was the amount of socio-political comment included - from the sensible suggestion to reduce the cost of drugs for poor nations to proposing a conspiracy theory to explain the availability of AIDS drugs. In addition, some statements propagate fallacies such as the case of the Monarch butterfly and Bt genes in corn.

I found that what made this book so useful was the sheer number of tables giving an idea as to the complexity, natural functions, applications and syntheses of natural products. The amount of time taken to amass the information for these tables must have been immense. As a whole the book could do with a good deal of copy editing, better typesetting and refinement of the diagrams. With this in mind, and the extension of some sections of the book and the removal of some unnecessary material, the second edition of this book should be excellent.

Marcel Jaspars
Aberdeen University, UK

Alkaloids – Nature's Curse or Blessing?

Manfred Hesse, Wiley-VCH, UK, 2002, xii + 413 pp., price £75, ISBN 3906390241 Search PubMedThe one question not answered in this otherwise excellent book is – ‘Curse or Blessing?’ Most police forces would undoubtedly claim that cocaine and heroin were a curse, though the value of these alkaloids as local anaesthetic and analgetic are beyond dispute. Comparison of use and abuse quickly becomes tedious, and a contemporary view would surely err on the positive side. While the number of naturally occurring alkaloids in clinical use is relatively small – morphine, vinblastine, vincristine, quinine, and a few others – many alkaloids have provided the skeletal basis for the design of pharmacologically more useful compounds, e.g. pethidine, buprenorphine, verapamil, mefloquine, etc. After a decade of dedication to combichem., the pharmaceutical industry is rediscovering the benefits of using Nature's own two billion year exploration of combichem. in higher plants, to identify key alkaloids (and other natural products) as lead structures for drug discovery.

Manfred Hesse is eminently qualified to write about alkaloids having spent much of his life working with them. His great knowledge and affection for this class of natural products shines through every page. He begins with a fascinating etymology of the word alkaloid and provides a masterly 100 page classification of this family. Indeed this chapter and the next one on structure elucidation could stand alone as a comprehensive introduction to the area. The classical methods of structure determination are illustrated by the 19^th century work on coniine, and the elucidation of the structure of villalstonine is used to show how modern techniques are used to solve complex structures. There is an amusing interlude for a discussion of artefacts produced during isolation or purification of alkaloids, and the chiroptical properties of alkaloids also merit a short chapter; then the second half of the book is devoted to synthesis, chemotaxonomy, biogenesis, and the biological–ethnopharmacological importance of alkaloids. This should be the best part of the book, but although the chemotaxonomy is very good, the chapters on synthesis and biogenesis are very selective. Almost all of the illustrative syntheses are 25 or more years old, so the reader gets no idea of the elegant chemistry that is used in contemporary alkaloid synthesis; and only the biogenesis of the benzylisoquinoline alkaloids is described.

The last three chapters cover the biological significance of alkaloids, some historical aspects (mainly brief mention of the main pioneers – Serturner, Pelletier, Robinson, Woodward, etc.), and a long account of those alkaloids that have particular cultural significance. This last chapter is particularly good and beautifully illustrated. All of the old favourites are discussed: hemlock, fly agaric, ergot, opium etc., with a lot of quotations from historical sources and superb figures.

Overall this is a very personal account of the alkaloids and could best be described as a very handsome book for the coffee table rather than one for the reference library.

John Mann
Queen's University, Belfast, UK

Biochemical Methods - A concise guide for students and researchers

A Pingoud, C. Urbanke, J. Hoggett and A. Jeltsch, Wiley–VCH, UK, 2002, 360 + xiii pp., price £45, ISBN 3-527-30299-9 Search PubMedThis updated version of ‘Biochemical Methods - A concise guide for students and researchers’ is a translation of the German version published in 1997. The authors have set themselves the ambitious task of providing a timely overview of all the disparate techniques used in Biochemistry and allied sciences. There is certainly a gap in coverage between text books on the science of Biochemistry and books containing protocols of the various techniques, and this book fills this gap extremely well. The book is very readable and is divided into 9 chapters, with most chapters having a reference list at the end of it containing important papers from the primary literature, recent reviews and monographs. This allows easy access to the methods for those who may wish to use them, and this is probably one of the most useful aspects of the book.

The book starts with a useful annotated bibliography of the various types of Biochemical literature, although the amount of material devoted to online literature searches and journals is quite small considering the importance of these resources. The book then goes on to cover some basic aspects of biochemical practice, data storage and safety considerations. The real meat of the book is then contained in the next 5 chapters, which covers the preparation of cell extracts, chromatography and other separation techniques, analytical methods, immunological methods and biophysical methods. This part of the book is really well written, with good explanations of how each of the various methods work. Despite been a ‘concise’ guide, these chapters manage to cover all of the important techniques ranging from those found in classical biochemistry (e.g. equilibrium dialysis, chemical modification of proteins) to cutting edge technologies (e.g. protein sequencing by mass spectrometry). The broad remit of this book means that the coverage of material is somewhat selective, but the authors manage to maintain a good balance between coverage of the techniques and clarity. There is good use of diagrams, which are a mixture of illustrations of the techniques and chemical mechanisms for the various processes. However, one minor criticism is that because the book is organised by technique it is sometimes necessary to read several sections in order to obtain complete information.

The final two chapters of the book (8 and 9) are devoted to analysis of biochemical data from various common experiments and the application of statistics to biochemical systems. Chapter 8 also contains an informative discussion on the algorithms used for database searches and sequence alignments using the FASTA and the Needleman and Wunsch methods. The authors point out that statistics are an important and somewhat neglected area of biochemistry, and discuss some basic statistics before introducing the ideas of model selection and error analysis. These themes are then developed using a number of ‘typical’ experiments, such as association and dissociation kinetics, binding in various types of systems, Michaelis–Menten kinetics, pre-steady-state kinetics, pH profiles and competition experiments. These chapters are at a considerably higher level than that typically taught in undergraduate biochemistry courses, but are at least able to convey the important principles. The CD associated with chapter 9 gives ‘hand-on’ experience of manipulating data in Microsoft Excel and model answers and these should allow the user to choose which methods are most applicable when designing and carrying out their own experiments.

This text is most suitable for post-graduate students in Biochemistry and related disciplines and established workers who want an overview of techniques from outside their specialist fields, although some chapters would be of benefit to second or third year undergraduates. It is a good starting point for anyone contemplating biochemical experiments, and the references will allow access to further reading on how to carry out the various techniques. Over all I consider it to be an excellent handbook and reference work and I will certainly be using it.

M. D. Lloyd
Department of Pharmacy & Pharmacology, University of Bath, UK

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