Book Reviews

Cytokine Inhibitors. Edited by Gennaro Cilibertoand Rocco Savino. Marcel Dekker, New York. 2001. xiv+ 372 pp. 15.5 × 23.5 cm. ISBN 0-0434-7. $165.00.

Reviewers usually complain about books in whicheach chapter has a different authorsthere is no conti-nuity from one chapter to the next. But cytokines are agroup of small signaling proteins which have numerous,sometimes opposing effects and complex interactions.They are so diverse that perhaps one should not expectcontinuity between chapters; cytokines may be a perfectjustification for a multiauthored book.

This book covers a wide range of topics. Cytokinesinclude the interleukins, tumor necrosis factors, avariety of growth factors, and colony-stimulating factors.They have been implicated in many disease states,including rheumatoid arthritis, graft vs host disease,Crohn’s disease, allergy, asthma, cardiovascular disease,cancer/tumor angiogenesis, and HIV infection. While afew chapters focus mainly on the cytokines and theireffects, most of the chapters take the next step, discuss-ing drugs which may inhibit the cytokines. There is afair amount of bioactivity and structure-activity infor-mation presented. Drug targets include the cytokinesthemselves, their receptors, and their converting en-zymes.

Overall, the book is well-produced. There are few ty-pographical or grammatical errors, the typesetting andlayout are clear, and the illustrations are well-done. Itappears that the editors were quite thorough in ensur-ing that the authors defined their jargon and acronymson the first use in each chapter. Most chapters includeliterature references through 1998; a few include 1999papers, and Chapter 11 includes a 2000 reference. Atthe other extreme, Chapter 5 covers literature as earlyas 1893. This book would be especially useful to medici-nal chemists who are new to the field of cytokines orthose who want to look at a broader range of cytokines.

D. Eric WaltersDepartment of Biochemistry and Molecular Biology

Finch University of Health Sciences/The Chicago Medical School

3333 Green Bay RoadNorth Chicago, Illinois 60064

JM010110W

10.1021/jm010110w

Solid Phase Synthesis.. Edited by Kevin Burgess.Wiley Interscience, New York. 2000. xiv + 277 pp. 15.5× 23.5 cm. ISBN 0471318256. $69.95.

The explosion in the use of combinatorial chemistryin the pharmaceutical industry has necessitated thediscovery of novel and reliable methods for conductingsolid-phase transformations. This book is a compilationof reviews describing solid-phase techniques that havebeen developed for use in selected structural classes. Asstated by the editor, this book does not cover all of theimportant aspects of solid-phase synthesis. However, in

its eight chapters, it describes solid-phase approachesused to synthesize guanidines, benzofused heterocycles,phenylacetylene oligomers, and a number of naturalproducts. Also included is a chapter outlining the useof solid-phase supports to conduct palladium-catalyzedC-C bond formation using the Heck, Stille, and Suzukireactions. Chapter 5 is an excellent compilation ofmethods for using functionalized polymers to assist insolution-phase reactions (sequestering excess reagentsand byproducts, use of polymer-supported quenchingagents). Chapter 6 describes the application of radiation-grafted polymer surfaces to the synthesis of purines,guanidines, and polysaccharides, as well as generationof a number of functional groups. Perhaps the mostgenerally useful is Chapter 7, which describes currentmethods for using vibrational spectroscopy (FT-IR) tomonitor and optimize solid-phase synthetic transforma-tions. Although this book will probably be of greaterinterest to industrial medicinal chemists, it does providea valuable overview of the versatility and utility of solid-phase synthesis in any setting. In addition, the chaptersare well-referenced, and for this reason, this bookprovides an excellent starting point for chemists inter-ested in solid-phase organic synthesis. Certainly, thisbook should be considered as an addition to anymedicinal chemistry library.

Patrick M. Woster

Department of Pharmaceutical Sciences539 Shapero Hall

College of Pharmacy and Health SciencesWayne State University

Detroit, Michigan 48202

JM010111O

10.1021/jm010111o

Metal Ions in Biological Systems. Volume 38.Probing of Proteins by Metal Ions and TheirLow Molecular Weight Complexes. Edited byAstrid Sigel and Helmut Sigel. Marcel Dekker, NewYork. 2001. xlvii + 690 pp. 16 × 23.5 cm. ISBN 0-8247-0289-1. $250.00.

This extremely well-bound book contains yet anothertimely presentation of current essential metalloelement(primarily Ca, Cu, Fe, and Zn) research dealing withtopics of special interest to medicinal chemists, bio-chemists, and others concerned with metalloelementphysical and coordination chemistry in biological sys-tems. At the onset it is pointed out that the remarkablestability of the amide bond and the phosphodiester bondgives rise to proteins and polynucleotides with half-livesestimated to be hundreds and one hundred millionyears, respectively, in physiological solution at neutralpH. Thus there are specific essential metalloelement-dependent enzymes required to catalyze specific proteinbond and nucleotide bond hydrolysis as well as bondformation in enabling normal chemical protease andnuclease or synthetic transformations that are ongoing

4304 Journal of Medicinal Chemistry, 2001, Vol. 44, No. 24 Book Reviews

in biochemical systems. The importance of metalloele-ment-dependent enzymes in the synthesis of peptidesand polydesoxy and polyribonucleic acid syntheses andrepair is also mentioned. It is remarkable that naturehas fashioned ligands that increase the rate of essentialmetalloelement-dependent catalytic activity by manyorders of magnitude and that these ligands protectbiochemical systems from undesirable chemical conse-quences associated with the presence of free ionicbonded metalloelements. Small molecular mass es-sential metalloelement chelates are presented as activesite enzyme mimetics in attempts to fashion chelatesthat might serve as useful agents capable of catalyzingreactions of interest in the development of new drugsand in gaining mechanistic understanding of essentialmetalloelement-dependent enzymes. As it turns out, theuse of alkaline earth and transition essential metallo-elements or nonessential metalloelements as ligands ofinterest is described in the synthesis of useful com-pounds that provide an understanding of known es-sential metalloelement-dependent enzyme catalases.There is also a substantial chapter dealing with electrontransfer proteins and with what is described as “su-pramolecular” (involving rather large ligands) approachto modeling electron transfer and oxygen activationproteins.

In general, the preferred use of metalloelement oxida-tion state is employed by most of the authors; however,there is occasional use of plus charged species in thecontext of metalloelements bonded to ligands via coor-dinate covalent bonds. While most chemists will under-stand this, many biologists may have difficulty under-standing that cationic species do not exist free of ananion. Another distraction is the use of the words “bind”,“binding”, “bound”, and even “bounded” for some formof the word “bond”, whether or not the exact characterof electronic bonding interaction is known.

John R. J. SorensonDivision of Medicinal Chemistry

Department of Pharmaceutical SciencesUniversity of Arkansas Medical Sciences Campus

Little Rock, Arkansas 72205-7122

JM010166Q

10.1021/jm010166q

Advances in Protein Chemistry. Volume 56. DrugDiscovery and Design. Edited by Edward M. Scolnick.Academic Press, San Diego, CA. 2000. xi + 567 pp. 16× 23.5 cm. ISBN 0-12-034256-1. $119.95.

This book consists of 11 chapters. An introductorychapter on the role of clinical trials in defining newchemical entities sets a context for the remaining 10chapters. Each of the later chapters offers a currentperspective on a case history in drug design anddiscovery. Collectively the chapter topics chosen repre-sent clinically important drug discoveries. Some of thestories are classics, well-known to medicinal chemists.The topics covered include angiotensin-converting en-zyme inhibitors, HMG-CoA- reductase inhibitors, cy-clooxygenase-2 inhibitors, 5a-reductase inhibitors, per-oxisome proliferator activated receptor agonists, HIV 1

protease inhibitors, calicurin inhibitors, selective estro-gen modulators, monoclonal antibody therapy, andglucan synthase inhibitors. While the emphasis isdecidedly not on telling the underlying chemical storyof the design of such agents, most of the individualchapters nevertheless make interesting reading. Thefocus of most of the chapters is on the clinical evaluationof drugs or drug candidates that are providing increas-ing efficacy or selectivity of action. Nowhere are thereextensive chemical discussions of SAR or of the underly-ing chemical approaches taken in drug design. Rather,the focus is on the drug targets and also on the valueto the drug discovery process of an understanding of thebiological regulation of the drug target. Structures ofdrugs or drug candidates are provided in some of thechapters, but details on the chemical design perspectiveare generally absent. That having been said, the readershould not take these comments as a serious criticismof the text, since the medicinal chemistry and drugdesign aspects of drug discovery have already beenreviewed elsewhere and these references are cited in theearly sections of some of the chapters. This volume willbe of interest to medicinal chemists, particularly thoseinvolved in drug discovery programs. Most chaptersmake clear what kinds of ideal agents are desired andprogress toward the goal of designing such agents. Ingeneral, the problems associated with less-specificearlier generation agents, from lack of receptor subtypeselectivity to unexpected ease in the development ofdrug resistance as well as the absence of such difficultiesin the newer agents, are discussed. Perhaps among themost interesting lessons to be learned from this text isthat we are asking a lot from the drug design anddiscovery process, and that we are very often able todeliver.

Richard A. Hudson

Graduate SchoolThe University of ToledoToledo, Ohio 43606-3390

JM010380E

10.1021/jm010380e

Solid Phase Synthesis: A Practical Guide. Editedby Steven A. Kates and Fernando Albericio. MarcelDekker, Inc., New York. 2000. xx + 826 pp. 15.5 × 24cm. ISBN 0-8247-0359-6. $250.00.

It was a pleasant surprise to see two such capablechemists take on the monumental task of offering apractical guide to the solid-phase synthesis of peptides,oligonucleotides, oligosaccharides, glycopeptides, oligo-nucleotide-peptide conjugates, and their derivatives.Included in this ambitious venture are chapters on resinchemistry, convergent (segment condensation) methodsfor the preparation of large proteins, combinatorialchemistry using peptides and amino acids, a review oninstrumentation for automated synthesis, peptide puri-fication and analysis, and the chromatographic analysisof combinatorial arrays (HPLC-MS). In general, Katesand Albericio do an excellent job of selecting hot topicsand reputable authors for the (14 out of 20) chapters

Journal of Medicinal Chemistry, 2001, Vol. 44, No. 24 4305

covering aspects of solid-phase peptide synthesis whichis, after all, the primary field whence other topics haveblossomed.

As a researcher who trained both with R. B. Merrifield(the pioneering peptide chemist at Rockefeller Univer-sity, who wrote an excellent Forward to the volume) andRobert L. Letsinger (the pioneering oligonucleotidechemist at Northwestern University), I feel compelledto mention that oligonucleotide chemistry was notcovered in equivalent depth to peptide chemistry in thisvolume. In all fairness, I suspect that if the authors hadtried for equal depth of coverage in all subjects, thisexcellent volume would have of necessity become aseries of volumes. Despite this small limitation, the bookprovides the most comprehensive, authoritative, and up-to-date coverage of solid-phase synthesis that I have yetseen. One of the book’s great strengths is the attentionto detail and the practical orientation of the articles.This ensures that practitioners of the art will want tokeep it close at hand for constant reference.

Lenore M. MartinDepartment of Biochemistry, Microbiology,

and Molecular GeneticsThe University of Rhode IslandKingston, Rhode Island 02881

JM010429G

10.1021/jm010429g

Combinatorial Chemistry. Edited by Hicham Fen-niri. Oxford University Press, Inc., New York. 2000.xxxii + 476 pp. 19 × 24.5 cm. ISBN 0-19-963754-7.$70.00 (paperback).

This book’s stated objective is to provide students witha text that will serve as an introductory reference tokey methods of combinatorial library generation andprocedures for library screening. In addition, the editorhoped to provide a review of the application of thesetechnologies to drug, catalyst, and materials discoveryand development. The approximately 500-page volumemore than meets its goals, and it will serve as a usefulreference to both student and researcher, its main valueto the latter being to provide insight into the application

of familiar technologies in fields other than those of one’sprimary interest. The book consists of 16 chapters, eachwritten by recognized leaders in the field and eachcovering a key aspect of combinatorial technology. Allcommon methods of solid- and solution-phase librarygeneration are reviewed, including directed sortedtechniques and positionally addressable library synthe-sis on continuous membranes. A condensed but exten-sive review of organic reactions performed on solidphase is also provided, with additional chapters coveringmulticomponent reactions used for library generation,and a timely review of multistep solution-phase com-binatorial synthesis. Combinatorial methods for thediscovery and optimization of electrocatalysts and com-binatorial approaches to the identification of chiralcatalysts significantly extend the scope of the text.Rounding out this extensive review is a discussion ofthe application of automation methods to combinatorialsynthesis. All chapters provide well-referenced bibliog-raphies covering the literature up to 1999, and anextensive general index provides ready access to all ofthe salient aspects of each of the topics reviewed in thegeneral text. Overall, this book is very well balanced,providing sufficient coverage of each of the topicsdiscussed to introduce all of the key aspects of theconcept. In addition, an extremely useful feature is theinclusion throughout most chapters of a series ofexperimental protocols, which provide a practical frame-work onto which the newly introduced concepts can behung. Importantly, the experiments described can forthe most part be conducted in an academic laboratorywithout the need for specialized equipment typicallyfound only in industrial locales. In conclusion, I foundthis book to be one of the most useful texts recentlyproduced in this field, and I would strongly recommendit to both student and practitioner alike.

Robert G. GentlesSenior Group Leader

Medicinal Chemistry TechnologiesGlobal Pharmaceutical Research and Development

Abbott LaboratoriesAbbott Park, Illinois 60044-3500

JM010342V

10.1021/jm010342v

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