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Book Reviews
Book Reviews Oligonucleotide Synthesis. Methods and Applications. Edited by Piet Herdewijn. Humana Press, Totowa, NJ. 2004. xi + 435 pp. 15.5 × 23.5 cm. ISBN 1-588-29-233-9. $125.00. “Oligonucleotide Synthesis. Methods and Applications” is a new addition to the Methods in Molecular Biology series. As such, it contains a number of chapters that provide detailed protocols that will be of use to practitioners in the field. The book covers a range of topics, from alternative sulfurizing reagents to synthetic processes for oligoribonucleotides containing hypermethylated bases. It also attempts to deal with issues such as identification of optimal sites for antisense agent binding in RNA and siRNA methods and applications. Several useful chapters deal with oligonucleotide synthesis. Caruthers and colleagues discuss a two-step process for DNA synthesis; a new thiation reagent is discussed by Sanvi and Colleagues; and a number of chapters discuss improved approaches to synthesis of RNA. Also included is a chapter on H-phosphonate chemistry. All of these chapters are useful, but I find it disappointing that there is no chapter that considers large-scale manufacturing or advances in analytical methods. Also helpful to the reader would be a chapter that reviews the different approaches to large- and small-scale oligonucleotide synthesis and considers the progress made and challenges that remain. It is in fact remarkable that oligonucleotide chemistry (phosphorothiote oligiodioxy nucleotides), which supports the one antisense drug marketed and the compounds used to treat more than 5000 patiients), is not dealt with as a topic. Nor are the manufacturing and analytical approaches and challenges associated with morpholinos (another chemistry supporting drugs in clinical trials) discussed. In short, while I find the chapters of value, I think that the lack of an overview, the failure to deal with large-scale synthesis and analysis, and a general lack of an organized attempt to place the entire field in context limit the value of the book. There is another group of chapters that deals with selected modifications such as LNA and PNA. Again, I feel that the chapters are fine, but the lack of an overview, the limited number of chemistries covered, and the lack of organization could actually mislead an uninformed reader about the scope of oligonucleotide medicinal chemistry and the place of various modifications in that broad field. Additionally, there are a few chapters that attempt to deal with the biological and pharmacological effects of various selected chemistries. In general, these chapters range from being irrelevant to being of limited value. Again, there is no overview, and there seems to be no logic for the selection of the topics. On balance, I feel that this book is a compendium of useful information that seems randomly chosen and consequently
provides a very narrow and potentially misleading overall picture of an exciting and complex field. Stanley Crooke Isis Pharmaceuticals, Inc. 2292 Faraday Avenue Carlsbad, California 92008 JM058178P 10.1021/jm058178p
Pseudo-Peptides in Drug Discovery. Edited by Peter E. Nielsen. Wiley-VCH, Weinheim, Germany. 2004. xiii + 244 pp. 17.5 × 24.5 cm. ISBN 3527306331. $125.00. Pseudo-peptides are defined by the editor of this book as “polyamides composed of amino acids other than R-amino acids”. By this definition, this book is a collection of six chapters on six topics written by top experts in their respective areas, not all of which fit this definition. The first chapter covers oligo (N-substituted) glycines (an R-amino acid) with particular emphasis on peptide mimetic aspects. This is an old area of peptide chemistry, and this chapter covers the most recent developments. Chapter 2 covers β- and γ-peptides. This chapter provides a comprehensive overview of all aspects of this exciting area including synthesis, structure, conformation, and bioactivity, including a brief discussion of the historical background. Chapter 3 provides a very succinct review of the use of pyrrole-imidazole polyamides which can specifically interact with nucleic acids. This chapter does an excellent job in discussing the structural and mechanistic context of work in this area. Chapter 4 covers peptide nucleic acids (PNAs). These are hybrid chemical structures of amino acids, primarily aminoethylglycine polyamides, and heterocyclic nucleobases in such a manner as to give structures complementary to nucleic acids that can serve as targets for both RNA and DNA. Not much is discussed regarding synthetic aspects, but rather, structural aspects and their relationships to potential drug applications are emphasized. Chapter 5 covers R-helical peptide nucleic acids (RPNAs) as a specific topic closely related to Chapter 4, but utilizing an R-amino acid containing R-helix motif to place the nucleotide heterocyclic nucleic acid groups, properly spaced, on the R-helical peptide. Some synthetic aspects are discussed, but again, the emphasis is on the chemical/physical and biochemical properties of these interesting structures. Chapter 6 claims to discuss DNA- and RNA-cleaving pseudo-peptides, but most of the review discusses R-amino acid containing peptides (and proteins) that can potentially cleave DNAs and RNAs. Critical comments of others’ work are found from time to time in the various reviews. Of course, there is much to criticize when newer methods are applied to complex cellular or whole animal effects, and most of the criticisms are well placed. However, in some cases the
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authors are not equally self-critical, so one is left to one’s own judgments about interpretation of some of the biological results obtained with the powerful new chemical tools that pseudo-peptides have made available. In this regard, it would have been useful if each chapter contained a critical analysis from synthetic, chemical, three-dimensional structure, dynamic, biochemical, pharmacological, and physiological perspectives regarding the potential of these new chemical tools, as well as their potential pitfalls, and the controls that one should use when these compounds are applied to biological systems. In particular, since these chapters specifically address pseudo-peptides, a more thorough discussion of the extent to which structures do (or can) mimic actual bioactive peptides would have been very useful, especially for readers who might be less familiar with developments in these areas but are anxious to use these tools. Despite these minor criticisms, the editor of this book has brought together a number of excellent reviews for obtaining up-to-date information in the areas of research covered, and I highly recommend it. The cost is quite steep for many individuals, but libraries at any university, medical center, or company that have research interests in peptide, peptidomimetic, and protein chemistry, biology, and medicine should have a copy.
quantitative structure-activity relationships (QSARs), Chapter 5; inhibitor/metal complexes, Chapter 6) and nonsulfonamide-type inhibitors (Chapter 7). A large number of structures, synthetic schemes, QSAR equations, and tables conveniently summarize the information that is provided for these topics. The editors have recognized the importance of carbonic anhydrases by including four chapters on the clinical applications of inhibitors in ophthalmology (Chapter 8), cancer (Chapter 9), gastroenterology/nephrology/neurology (Chapter 10), and dermatology (Chapter 11). An interesting phenomenon associated with the carbonic anhydrases is that these enzymes can be susceptible to activation. The mechanism, isozyme specificity, required structural features (particularly in comparison to inhibition), and potential consequences of activation are described in Chapter 12.
Victor J. Hruby Department of Chemistry University of Arizona Tucson, Arizona 85721 JM0581765
Overall, the editors have done a fine job of condensing extensive information about carbonic anhydrases into a single volume. This book should be of interest and value to anyone working in this field. Peter J. Harvison Department of Pharmaceutical Sciences Philadelphia College of Pharmacy University of the Sciences in Philadelphia Philadelphia, Pennsylvania 19104 JM058187Y 10.1021/jm058187y
10.1021/jm0581765
Carbonic Anhydrase. Its Inhibitors and Activators. CRC Enzyme Inhibitors Series. Edited by Claudiu T. Supuran, Andrea Scozzafava, and Janet Conway. CRC Press, Boca Rotan, FL. 2004. ix + 363 pp. 16 × 23 cm. ISBN 0-415-30673-6. $138.95. This book consists of 12 chapters that provide comprehensive reviews of carbonic anhydrases. The chapters are extensively referenced and well illustrated. Citations in most of the chapters are dated through 2003 (or 2004 in a few cases). Color versions of several figures are provided, and these are generally of better quality and easier to view than the corresponding gray scale illustrations. A thorough subject index is included. Chapter 1 provides a concise but useful summary of this versatile family of enzymes. The biochemistry (i.e., catalytic mechanism and isozyme classification) and physiology (i.e., function and distribution) are described. The poorly understood noncatalytic carbonic anhydrase related proteins are briefly mentioned here and more thoroughly in Chapter 2. Together, these two chapters comprise a useful introduction to the carbonic anhydrases, especially for readers who are not familiar with this topic. The concept of carbonic anhydrase inhibitors, a major focus of this book, is explored in five chapters. Chapter 3 described the multiple binding modes that are associated with several inhibitors. The next four chapters are then devoted to the prototypical sulfonamide inhibitors (synthesis and development, Chapter 4;
Annual Review of Biochemistry. Volume 73. Edited by Charles C. Richardson, Roger D. Komrnberg, Christian R. H. Raetz, and Jeremy W. Thomrner. Annual Reviews, Palo Alto, CA. 2004. x + 1232 pp. 16 × 23.5 cm. ISBN 0-8243-0873-5. $84.00. This book is the 73rd volume of this long-standing series. This particular volume consists of 33 reviews written by individuals and groups of authors. A variety of current topics in biochemistry is included, ranging from DNA repair to the role of N-linked glycans. The book also contains a list of related articles from other Annual Reviews, as well as author and subject indices. All of the reviews are well-written, interesting, and informative. However, only some of the chapters are likely to be of direct interest to medicinal chemists: (1) Pyridoxyl Phosphate Enzymes: Mechanistic, Structural, and Evolutionary Considerations; (2) Inositol 1,4,5Triphosphate Receptors as Signal Integrators; (3) Structure and Function of TolC: The Bacterial Exit Duct for Proteins and Drugs; (4) Palmitoylation of Intracellular Signaling Proteins: Regulation and Function; (5) Structural Aspects of Ligand Binding to and Electron Transfer in Bacterial and Fungal P450s; (6) Roles of N-linked Glycans in the Endoplasmic Reticulum; (7) Opioid Receptors. The present volume is a welcome addition to the series in library collections. Individual medicinal chem-
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ists may want this book in their personal collection if the reviews cited above are of utility in their research efforts.
bocation reactions. Chapters by H. Schmidbaur and C. Merlic provide a taste of the unusual chemistry of metal coordinated carbocations. Laali’s contribution on cations of polynuclear aromatics provides insight into a potential role for carbocations in carcinogenesis. Of course, no text on the chemistry of carbocations would be complete without directly addressing the synthetic aspects of superacid chemistry; in this text, Jean-Claude Jacquery does the honors. The references in many of the articles are very current, and the indexing is good. There is something in this book for everyone interested in the carbocation chemistry: neophyte, student, chemical historian, or specialist. This book will be a welcome addition to any library that serves a scientific community.
Thomas E. Prisinzano Division of Medicinal and Natural Products Chemistry College of Pharmacy The University of Iowa Iowa City, Iowa 52242 JM058195E 10.1021/jm058195e
Carbocation Chemistry. Edited by George A. Olah and G. K. Surya Prakash. Wiley Interscience, New York. 2004. x + 393 pp. 16 × 24 cm. ISBN 041284904. $99.95. In 1901 the Norris and Kehrmann laboratories independently reported studies on the chemistry of the triphenylmethyl cation. It is appealing to speculate whether either group appreciated the depth and breadth of the body of chemistry that their work would engender. In June 2001, the Laker Hydrocarbon Research Institute sponsored a “100 Year Festschrift” celebrating the first century of carbocation chemistry. Carbocation Chemistry is a collection of 14 papers selected from the presentations at the centennial symposium. Each chapter is the result of a stand-alone lecture presented at the Loker Hydrocarbon Research Institute Symposium. Many of the chapters read like the reminiscences of veterans, told with fondness and candor. This book is a good source of current information on the state of the art of carbocation chemistry, yet it also honors the historic research upon which the state of the art rests. The articles cover a broad range of carbocation-related topics. The book begins with a very well written historical perspective from Peter Stang. Starting with the initial reports from the Norris and Kehrmann labs, Stang takes the reader on an enjoyable, though rapid, tour of the many new ideas, technologies, and controversies that characterized the first 100 years of carbocations. This sets the stage for Olah’s chapter, which is a more comprehensive overview. In this chapter Olah describes general methods for their synthesis, the development of methods for their study, the “nonclassical” ion controversy that these data engendered, as well as studies on higher order cations. This chapter is written from the unique perspective of a major player in the field and could serve as a primer on carbocations on its own. Later chapters describe more specialized areas of cation research written by leaders in the field such as Paul Von Ragure´ Schleyer (neutral and anionic zwitterionic systems), G. K. Surya Prakash (chemistry of long-lived mono- and dications), a topic upon which he and Professor Olah have collaborated for many years, and V. G. Shubin and G. I. Borodkin (research on long-lived cations done under the aegis of the late Professor V. A. Koptyug at the Institute for Organic Chemistry in Novosibirsk). Much of this last work had never been described in an English language article. Several later chapters describe the use of spectroscopy and physical organic methods to characterize the kinetics, stereochemical influences, and mechanism of “typical” car-
Thomas J. Caggiano Wyeth Research CN 8000 Princeton, New Jersey 08543-8000 JM0581922 10.1021/jm0581922
Enzymes and Their Inhibition. Drug Development. Edited by H. John Smith and Claire Simons. CRC Press, Boca Raton, FL. 2005. xi + 308 pp. 16 × 24 cm. ISBN 0-4153-3402-0. £85.00. This book consists of five chapters. The first four deal with basic and essential concepts of enzymology, such as enzyme structure and function, chemical mechanisms of catalysis, steady-state kinetics measurements, and the various classes of enzyme inhibitors. Although much of this background information can be found in other reference books and will not be useful to a well-trained enzymologist, the presentation and examples have value because they focus on drug targets (carbonic anhydrase, proteases) or enzymes that play a critical role in drug metabolism (cytochrome P450). Thus, the first four chapters provide a reasonable foundation for the final chapter, which deals with the development of enzyme inhibitors as drugs and comprises nearly one-half of the entire book. The final topics include the selection of an enzymatic drug target, the rational design of an inhibitor based on the catalytic mechanism or modification of a lead inhibitor, and the process of bringing a drug candidate from the bench to the marketplace. This chapter has significant value as a reference text for graduate students who have an interest in pharmacology or for trained enzymologists who are interested in inhibitor design but who are less familiar with the more extensive considerations of drug development. This chapter consists of selected examples from the areas of endocrine therapy of breast and prostate cancer and inhibitors that target proteases (HIV-protease, thrombin, metalloproteinases). A shortcoming in this chapter is that newer drug targets such as the proteosome and protein kinases are not discussed nor are new areas of inhibitor development such as “tethering” and “click” chemistry. This book will have value as a focused reference text for graduate students in pharmacology and enzymology. The various subjects are covered clearly and concisely
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with adequate referencing, which should allow students to quickly obtain a broad overview of concepts in enzyme inhibitor development, and also to provide a window into more extensive literature in this area.
Probably the most interesting discussion in the work considers the topic of creativity. Here, one can agree with the authors that it is an “often neglected question” in the graduate curriculum, and one can enjoy their review of the many aspects of creativity. And yet, as in Mark Twain’s famous aphorism about the weather, talking about creativity does not lead to doing anything about it. In the end, the authors come to a longrecognized conclusion: decisions on where to find creative and enjoyable work should be based on “local factors”sthe institution, the community, clever and innovative colleagues and advisors, and an exciting and well-funded research area. The remaining five chapters of the book then provide well-considered advice on the various aspects of oral presentations, the culture and ethics of scientific publishing, preparing a publication, electronic publication, and patents. Certainly this is laudable, but at the same time one has to wonder if one more exhortation to speakers to make readable slides or to authors to “show a draft of your paper to colleagues and ask for their comments” will finally have its intended effect. One has to believe that mere existence as a student in a graduate department results in the awareness of such information but not necessarily in its acceptance. The final chapter provides a brief but useful overview of the fundamentals of patents.
James Stivers Department of Pharmacology and Molecular Sciences Johns Hopkins School of Medicine WBSB 314 725 North Wolfe Street Baltimore, Maryland 21205 JM0581967 10.1021/jm0581967
Make Your Mark in Science. By Claus Ascheron and Angela Kickuth. Wiley, Hoboken, NJ. 2005. xiii + 235 pp. 14 × 20.5 cm. ISBN 0-471- 65733-6 (Paperback). $29.95. The authors of this softcover book are both Ph.D. physicists who are employed in the publishing industry. As they explain the preface, the book is intended to address “the often neglected questions of (1) how to work creatively once you have left the exams and the course books behind you, (2) how to effectively communicate your scientific achievements in oral presentations and written presentations, and (3) whether or how to protect your accomplishments with a patent”. The authors state further, “In contrast to [other] detail-laden tomes [on these topics], our aim when writing this text was to make it concise, enjoyable to read, and easy to digest.” This low-priced volume is attractively printed and produced by the publisher, but it has only a few references and no index. It is appropriate for graduate students and recent graduates, and it is reviewed here to inform their faculty and senior colleagues.
Manfred E. Wolff Intellepharm, Inc. 1304 Morningside Drive Laguna Beach, California 92651-2809 JM0582017 10.1021/jm0582017
