Downloaded by 80.82.77.83 on May 16, 2018 | https://pubs.acs.org Publication Date: May 30, 1991 | doi: 10.1021/bk-1991-0463.pr001
About the Cover
It wasn't possible to include both pieces of art on the cover, therefore they are printed here. The turtle representation of an inositol phosphate was generously provided by B . W. Agranoff and the artwork by Thomas F o r d - Holevinski. Steric relationships are conveniently visualized by employing the image of a turtle to represent the myoinositol molecule. For example, in D myo-inositol-l-phosphate, the head represents the axial hydroxyl at D2, while the four limbs and tail comprise the five equatorial groups. Viewed from above, the right front leg of the turtle is at D l and proceeding coun terclockwise, the head is D2, etc.
χ Reitz; Inositol Phosphates and Derivatives ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
Preface INOSITOL PHOSPHATES AND THEIR DERIVATIVES are remarkably versatile compounds, crucial for the transduction of information in living organisms. As with the formation of c-AMP by adenylate cyclase, phospholipase C-catalyzed cleavage of membrane-bound phosphatidylinositol triphosphate (PIP ) i myoinositol 1,4,5-triphosphate and diacylglycerol is a keenly important means of cellular signaling. Indeed, 28 of 74 receptors listed in the 1991 "Receptor Nomenclature Supplement" of Trends in Pharmacological Sciences are reported to be linked to an increase of P I P turnover following receptor activation. Key aspects of research in the general area of inositol phosphates and derivatives are highlighted in the book, especially from the viewpoint of synthetic organic chemistry, with contributions from biochemistry and pharmacology. Organic and medicinal chemists have synthesized the natural inositol phosphates to demonstrate unambiguously their structure. Additionally, these chemists have prepared a host of unnatural inositol phosphates, isosteres, and related derivatives in a search for selective and useful enzyme modulators. If the inositol phosphates and the pathways that create them are a ubiquitous means by which cells respond to extracellular stimuli, then how can one hope to obtain therapeutically useful selectivity for one system over another? There are a number of reasons to believe that this second-messenger pathway, like others, can be favorably manipulated in vivo. Enzymes have different tissue selective isoforms, such as phospholipase C, for which five isoforms are known. Receptors and enzymes have heterogeneous distributions. Other organ- or disease-specific factors may conspire to make selectivity possible. As our knowledge of fundamental biochemistry and pharmacology grows in this area, so also will our ability to conceive of approaches to intervene with advantage. Chemists have used a mixture of standard and novel methods to prepare inositol phosphates and derivatives. The synthetic challenges are formidable and include issues of stereocontrol, resolution of enantiomers, regioselectivity of reactions such as phosphorylations, and protecting group manipulations. Overall, this book provides a glimpse into the chemistry required to prepare the inositol phosphates and derivatives and into the uses to which such molecules are being put as enzyme inhibitors, biochemical tools, and potential pharmacological agents. This book is intended as a resource for n t o
Downloaded by 80.82.77.83 on May 16, 2018 | https://pubs.acs.org Publication Date: May 30, 1991 | doi: 10.1021/bk-1991-0463.pr001
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xi Reitz; Inositol Phosphates and Derivatives ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
scientists involved in the field of inositol phosphates and derivatives in academia and industry, as well as a broad reference for organic, medicinal, and carbohydrate chemists and biochemists who are generalists with a passing interest.
Downloaded by 80.82.77.83 on May 16, 2018 | https://pubs.acs.org Publication Date: May 30, 1991 | doi: 10.1021/bk-1991-0463.pr001
Acknowledgments I am grateful to the international group of authors whose chapters appear in this volume. I admire the diversity of the research they conducted, and I wish them the best of success in all future ventures. I hope this book will facilitate scientific interchange among these contributors and others, so that full use will be made of new discoveries related to the organic chemistry, biochemistry, and pharmacology of the inositol phosphates. Walter W. Zajac, Jr., of Villanova University and Anthony S. Serianni of the University of Notre Dame were among the helpful colleagues from the Division of Carbohydrate Chemistry of the American Chemical Society. Financial support was also provided by the donors of the Petroleum Research Fund, which is administered by the American Chemi cal Society; the R.W. Johnson Pharmaceutical Research Institute, a John son and Johnson Company; and Merck Sharp and Dohme Research Laboratories. I especially appreciate the assistance and suggestions of Roy Gigg and Joseph P. Vacca, who are authors of chapters in this book. The engaging turtle representation of an inositol phosphate shown on the cover was generously provided by B. W. Agranoff and the artwork by Thomas Ford-Holevinski. Even though myoinositol looks like a turtle, research has advanced in this area with the speed of a hare. One would hope that the myο -inositol turtle is of the mutant ninja variety so we can press on in the future. Special thanks are due also to Frank Eisenberg, Jr., who briefly came out of retirement to coauthor the first chapter, and whom I wish many years of skiing and travel. I applaud the efforts of all the reviewers who examined drafts of the enclosed chapters. I thank the R.W. Johnson Pharmaceutical Research Institute for the time and support they gave in the editing process. A . Maureen Rouhi, of the A C S Books Department, provided the needed insight and thoroughness required to bring this volume to print.
A L L E N B. REITZ R.W. Johnson Pharmaceutical Research Institute Spring House, P A 19477-0776 March 11, 1991 xii Reitz; Inositol Phosphates and Derivatives ACS Symposium Series; American Chemical Society: Washington, DC, 1991.
