book review: bionmr in drug research. edited by oliver zerbe

1
often accompanied by experimental data. Commercially available instru- ments for the measurements are also listed and briefly described. However, there is a certain amount of repetition between individual chapters, and this, as well as the lack of cross-references, makes the book difficult reading for the user who wants only a general overview of HTS. Both these faults are undoubtedly the result of the chapters having been written by different authors, thus ensuring the highest possi- ble standard of expertise for each area. The overlapping can also be an advant- age from the point of view of the researcher seeking the best solution for a particular problem, as it offers the possibility not only to look for an answer directly in the relevant chapter but also to gather as much information as possi- ble. That is certainly something that one expects from a “handbook”. Reinhold Müller Knoll GmbH Ludwigshafen (Germany) BioNMR in Drug Research Edited by Oliver Zerbe. (Series: Methods and Principles in Medicinal Chem- istry, Vol. 16. Series editors: R. Mannhold, H. Kubinyi, G. Folk- ers.) Wiley-VCH, Weinheim 2003. 484 pp., hardcover E 149.00.—ISBN 3-527-30465-7 The five main sections into which this book is divided range from basic tech- niques through modern methods of NMR spectroscopy to strategies for using NMR in drug research and devel- opment. The first section, “Basic Techni- ques”, consists of chapters on state-of- the-art methods for the expression of isotopically enriched proteins, auto- mated methods for structure determi- nation and molecular calculations, and new techniques for noise suppression and for obtaining enhanced NMR sen- sitivity. With regard to which of these three areas is most important, the answer certainly depends on one)s point of view. All three chapters are excellent, and each one includes an extensive bibliography for readers who need more details. In my view the chapter on expression of isotopically enriched proteins is especially informa- tive and valuable from a practical stand- point. It includes tables which present key information about established and newer expression systems in a clear and easily accessible form, enabling one to quickly grasp the essential features. This chapter has a central function in the book because methods for isotopic enrichment are a very important pre- requisite for drug research. The second section begins with a concise survey of different strategies for interpreting protein NMR spectra. That is followed by a chapter explaining important details of NMR spectroscopic investigations, especially as applied to membrane-associated peptides and pro- teins, and a chapter on NMR analysis of nucleic acids. In these chapters special emphasis is given to current develop- ments in the application of NMR spec- troscopy to studies of membrane pro- teins. The chapter concerned with mem- brane-associated peptides and proteins, which is titled “NMR Experiments in the Area of Drug Design”, is undoubt- edly the most exciting of the two, since this class of biomolecules, while still presenting difficult problems, also offers the most interesting targets in the search for new drugs. The third section of the book, “Modern Spectroscopic Techniques”, is the longest, which is not surprising in view of the many very interesting new methods that have been developed in recent years. The book certainly does full justice to those developments, describing in detail techniques such as cross-correlated relaxation, residual dipolar couplings, measurements of the scalar coupling through hydrogen bonds, the TROSY concept, and measurements of 15 N relaxation parameters. The chap- ter also includes a paragraph on solid- state MAS-NMR studies of isotopically enriched biological samples, thus recog- nizing the extent to which these techni- ques have become more widely used in the last few years. The last two sections of the book are titled “Tools for Investigation of Drug– Receptor Complexes and for Ligand Screening” and “Strategies for Drug Development Using NMR”. The many different aspects covered in these sec- tions include descriptions of techniques, automated procedures for identifying hits, and concepts such as the shapes strategy that are aimed at identifying lead structures. It is the last of these areas that is richest in examples of the application of NMR spectroscopy in drug design. Also, however, one of the most important strengths of NMR spec- troscopy as an aid to drug design is shown in a highly informative and clearly written chapter on “NMR of Weakly Binding Ligands”. The last chapter of the book is concerned with the application of NMR-supported drug design to very large protein molecules. The methods described in this chapter are based on the TROSY experiment, which links up neatly to the earlier more theoretical chapters in the book. The editor, Oliver Zerbe, has man- aged to recruit a team of well-recog- nized experts as authors for this book, thereby ensuring a high standard of (as they say in the news media) “reliable and objective reporting”. Bio-NMR in Drug Research is not only of interest to specialists in pharmaceutical research and development, but will certainly also be a valuable resource for everyone concerned with the latest methods of NMR spectroscopy and their applica- tions to biomolecules. Thomas Peters Institut fɒr Chemie UniversitȨt Lɒbeck (Germany) Books 3576 # 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.angewandte.org Angew. Chem. Int. Ed. 2003, 42, 3575 – 3577

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Page 1: Book Review: BioNMR in Drug Research. Edited by Oliver Zerbe

often accompanied by experimentaldata. Commercially available instru-ments for the measurements are alsolisted and briefly described. However,there is a certain amount of repetitionbetween individual chapters, and this, aswell as the lack of cross-references,makes the book difficult reading forthe user who wants only a generaloverview of HTS. Both these faults areundoubtedly the result of the chaptershaving been written by differentauthors, thus ensuring the highest possi-ble standard of expertise for each area.The overlapping can also be an advant-age from the point of view of theresearcher seeking the best solution fora particular problem, as it offers thepossibility not only to look for an answerdirectly in the relevant chapter but alsoto gather as much information as possi-ble. That is certainly something that oneexpects from a “handbook”.

Reinhold MllerKnoll GmbHLudwigshafen (Germany)

BioNMR in Drug Research

Edited by OliverZerbe. (Series:Methods andPrinciples inMedicinal Chem-istry, Vol. 16.Series editors: R.Mannhold, H.Kubinyi, G. Folk-ers.) Wiley-VCH,Weinheim 2003.

484 pp., hardcover E 149.00.—ISBN3-527-30465-7

The five main sections into which thisbook is divided range from basic tech-niques through modern methods ofNMR spectroscopy to strategies forusing NMR in drug research and devel-opment.

The first section, “Basic Techni-ques”, consists of chapters on state-of-the-art methods for the expression ofisotopically enriched proteins, auto-mated methods for structure determi-

nation and molecular calculations, andnew techniques for noise suppressionand for obtaining enhanced NMR sen-sitivity. With regard to which of thesethree areas is most important, theanswer certainly depends on one'spoint of view. All three chapters areexcellent, and each one includes anextensive bibliography for readers whoneed more details. In my view thechapter on expression of isotopicallyenriched proteins is especially informa-tive and valuable from a practical stand-point. It includes tables which presentkey information about established andnewer expression systems in a clear andeasily accessible form, enabling one toquickly grasp the essential features. Thischapter has a central function in thebook because methods for isotopicenrichment are a very important pre-requisite for drug research.

The second section begins with aconcise survey of different strategies forinterpreting protein NMR spectra. Thatis followed by a chapter explainingimportant details of NMR spectroscopicinvestigations, especially as applied tomembrane-associated peptides and pro-teins, and a chapter on NMR analysis ofnucleic acids. In these chapters specialemphasis is given to current develop-ments in the application of NMR spec-troscopy to studies of membrane pro-teins. The chapter concerned with mem-brane-associated peptides and proteins,which is titled “NMR Experiments inthe Area of Drug Design”, is undoubt-edly the most exciting of the two, sincethis class of biomolecules, while stillpresenting difficult problems, also offersthe most interesting targets in the searchfor new drugs.

The third section of the book,“Modern Spectroscopic Techniques”, isthe longest, which is not surprising inview of the many very interesting newmethods that have been developed inrecent years. The book certainly doesfull justice to those developments,describing in detail techniques such ascross-correlated relaxation, residualdipolar couplings, measurements of thescalar coupling through hydrogen bonds,the TROSY concept, and measurementsof 15N relaxation parameters. The chap-ter also includes a paragraph on solid-state MAS-NMR studies of isotopicallyenriched biological samples, thus recog-

nizing the extent to which these techni-ques have become more widely used inthe last few years.

The last two sections of the book aretitled “Tools for Investigation of Drug –Receptor Complexes and for LigandScreening” and “Strategies for DrugDevelopment Using NMR”. The manydifferent aspects covered in these sec-tions include descriptions of techniques,automated procedures for identifyinghits, and concepts such as the shapesstrategy that are aimed at identifyinglead structures. It is the last of theseareas that is richest in examples of theapplication of NMR spectroscopy indrug design. Also, however, one of themost important strengths of NMR spec-troscopy as an aid to drug design isshown in a highly informative andclearly written chapter on “NMR ofWeakly Binding Ligands”. The lastchapter of the book is concerned withthe application of NMR-supported drugdesign to very large protein molecules.The methods described in this chapterare based on the TROSY experiment,which links up neatly to the earlier moretheoretical chapters in the book.

The editor, Oliver Zerbe, has man-aged to recruit a team of well-recog-nized experts as authors for this book,thereby ensuring a high standard of (asthey say in the news media) “reliableand objective reporting”. Bio-NMR inDrug Research is not only of interest tospecialists in pharmaceutical researchand development, but will certainly alsobe a valuable resource for everyoneconcerned with the latest methods ofNMR spectroscopy and their applica-tions to biomolecules.

Thomas PetersInstitut f8r ChemieUniversit:t L8beck (Germany)

Books

3576 ; 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.angewandte.org Angew. Chem. Int. Ed. 2003, 42, 3575 – 3577