- Email: [email protected]
Nucleic acid targeted drug design
TiPS - October 1993 [Vol. 141
A synaptic dimension Ion Channels
Vol. 3
edited by Toshio Narahashi, Plenum Press, 1992. $75.00 (xv + 350 pages) ISBN 0 306 44166 7 This, the third volume of Ion Channels, further establishes the reputation of the series by giving a broad perspective, with the authors providing a detailed and personal view of their subjects. The book concentrates on the regulation of ligand-gated ion channels and aspects of their kinetics, but there are also chapters on voltage-sensitive Ca2+ channels, developmental aspects of K+ currents and neurogenetic studies of voltage-gated channels. This is complimented by chapters on axon terminal excitability and epilepsy and an elegant chapter on neural correlates of memory storage in Hermissenda, which helps link some of the more mechanistic strands in the book. The stated aim is to inform the general reader and specialist alike of new developments and current progress in the field. The field is immense, potentially extending well outside the traditional boundaries of ‘excitable tissues’ no doubt this is why such an uninformative title was originally selected. However, this volume is well and truly anchored in the nervous system. While there appears to have been some attempt to avoid a thematic approach, the topics are of particular relevance to synaptic transmission and mechanisms of plasticity. Although modulation of voltagegated currents in general and Ca2+ currents in particular will regulate transmitter release, most of the work presented here concerns modulation of postsynaptic receptors through phosphorylation by second cascades. messenger Taking the nicotinic acetylcholine receptor as the prototypical ligandgated channel, functional regulation by G proteins and kinases are examined. The general application of such regulation is implied by reference to GABAA receptor function, In addition, there is an interesting article on the gating of GABA* receptor ion channels, which includes data on regulation by barbiturates, benzodiazepines and steroids at the single channel level.
385 In the recent past, the development of methods enabling submillisecond control of agonist application has permitted analysis of channel activation and desensitization by glutamate receptors to be related to the timecourse of synaptic transmission. Using one such method, Dude], Franke and Hatt bring together work from vertebrates and invertebrates in an informative discussion of activation and fast desensitization of ligand-gated channels. On the down side, some of the molecular biology of K+ channels has dated quickly and the quanta1 data have been over-interpreted in the chapter on synaptic transmission mediated by amino acids.
But these are minor gripes - the great strength of this volume is the breadth of its outlook in bringing together related issues from voltage-gated to ligandgated receptors in both vertebrate and invertebrate preparations. As Toshio Narahashi reminds us in the preface, many therapeutic drugs exert their effects through interactions with ion channels. So for those of you interested in a synaptic dimension to your pharmacology, I can thoroughly recommend this book as an invaluable resource. I. D. FORSYTHE
Acid test
The text is a companion to Computer Aided Drxg Design and, as a result, the role of molecular modelling in drug design is emphasized throughout the book. However, there are also substantial sections devoted to X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy studies. The volume therefore mainly deals with the structural specifics of nucleic acid interactions, and encompasses both theoretical and experimental studies. The book is divided into two main sections, methods and applications, although the division seems somewhat artificial. In the methods section, chapters deal with the use of X-ray crystalNMR spectroscopy, lography, structure-activity quantitative relationships (QSAR), computational chemistry and footprinting techniques. These chapters contain introductory discussions and are illustrated by experimental cr theoretical data. The applications section presents more examples of nucleic acid interactions without the descriptions of the experimental methods. A wide range of nucleic acid complexes are discussed. These include a number of small-molecule intercalation and minorgroove complexes that bind both noncovalently. covalently and pyrrolo(l,4-benzoLexitropsins, diazepines, enediyne antibiotics, quinolones, anthraquinones and quinolines are all reviewed in avaiiable The some detail. crystalacid protein-nucleic
Nucleic Acid Targeted Design
Drug
edited by C. L. Fropst and Thomas !. Perun. Marcel Dekker, 1992. $265.00 (xiii + 644 pages) ISBN 0 8247 8662 9 The design, synthesis and characterization of molecules that interact with nucleic acids is currently an area of intense research. Nucleic acids have iong been a target for drug design as, for example, in the development of anthracyclines. However, in the past decade, substantial information has been obtained on the structural basis of ligand-nucleic acid, protein-nucleic acid and nucleic acid-nucleic acid interactions. Notable advances have also been made in the biological characterization of ternary complexes between drug molecules, nucleic acids and various enzymes and topoisomerases such as polymerases. Chemical advances have also fostered the development of modified nucleic acids that are capable of binding to complementary nucleic acid sequences with high affinity and specificity. These structural, biological and chemical advances have all focused new attention on nucleic acids as a target for drug design. Nucleic Acid Targeted Drug Design provides both an overview of the current understanding of nucleic acids as a target for drug design and a detailed analysis of certain nucleic acid-ligand and nucleic acid-protein interactions.
Department
of Physiology. Box 138,
Leicester, PO LEI 9HN.
University of Leicesfer, UK
TiPS - Ocfober 1993 [Vol. 141 data are also discussed extensively. Finally, ribozyme and antisense-antigene drug-design with strategies are discussed relevant examples. The book is a fairly comprehensive survey of the field of nucleic acid drug design, but one area of weakness is the lack of a focused discussion on the role of solvation-desolvation phenomena in the binding of ligands to nucleic acids. While the subject is mentioned at various points in the book, a specific analysis of sol-
lographic
New edition Annual Review of Pharmacology and Toxicology, Volume 33, 1993 edited by Arthur K. Cho, Terrence F. Elaschke, Horace N. ioh and jnmes L. Way, Annual Reviews, 2993. $44.00 in USA and Canada {~~9.#0 elsewhere) fvi f 696 pages) 1SBN 0 8243 01330 The quest for a cure, Gertrude B. Elion; Adventures in autopharmacology: a biographic view with digressions into other matters, M. 1. Rand; Calmodulin in neurotransmitter and hormone action, Margaret E. Gnegy; Pharmacology of the endothelium in ischemiareperfusion and circulatory shock, Allan M. Lefer and David I. Lefer; Antiinflammato~ peptide agonists, Edward T. Wei and golly A. Thomas; GABAB receptor pharmacology, Norman G. Bowery; HIV drug resistance, Douglas D. Richman; New antidepressants, Leo E. Holfister and lames L. C~aghorn; Recent studies on the structure and function of multisubstrate flavin-containing monooxygenases, D. M. Ziegler; Covalent modifications of Gproteins, Bernard Kwok-Keung rang and Harvey K. Yamane; Pharmacologic and therapeutic application of a2-adrenoceptor sL;btypes, Robert R. Ruffolo Jr, Andrew J. Nichols, jeffrey M. Stadel and 1. Paul Hieble; Molecular diversity of the dopamine receptors, Olivier Civelli, fames R. B~n~ow and David K. Grandy; Neuropeptide Y-related peptides and their receptors - are the receptors potential therapeutic drug targets?, Clazs Wahlestedt and Donald I. Reis; Effects of opioids on the hypothalam~pituita~-
and the corresponding hydrophobic effects would have been useful, given their critical role in both nucleic acid structure and interactions of nucleic acids with ligands. Another controversial area that could have been treated in more depth is the relative importance of electrostatic versus dispersion forces in governing the affinity and specificity of nucleic acid-l&and interactions. Both the above points are of particular interest to computational chemists involved in the
field of nucleic acid research. the book is recOverall, ommended both as an instructional text and as a reference; it is a good update of our current knowledge and understanding of nucleic acids as a target for drug design. In general, the text is clear, and the wealth of structural information summarized and discussed makes this worthwhile reading.
adrenal axis, Robert N. Pechnick; Respiratory tract uptake of inhalants and metabolism of xenobiotics, Alan R. Dahl and J. L. Lewis; Childhood lead poisoning and its treatment, Carol R. Angle; Renal toxicity of non-steroidal ~ti-inflammato~ drugs, M. D. Murray and D. Craig Brater; of Parkinson’s Pharmacology disease therapy: an update, Irwin J. Kopin; Cardiovascular toxicity of anabolic steroids, Robin W. Rockhold; Prodrugs of peptides and
proteins for improved formulation and delivery, Reza Oliyai and Valentine 1. Stella; Molecular and ionic mimicry of toxic metals, Clarkson; Gene Thomas W. therapy: concepts, current trials, and future directions, Paul Tolstoshev; The pharmacology of ATP-sensitive potassium channels, GilIian Edwards and A. H. Amphetamine: effects Weston; on catecholamine systems and behavior, Lewis S. Seiden, Karen E. Sabol and George A. Ricaurte.
vation
Books received Tim 1. Ahem and Mark C. Mannine (eds) Sfabiiify of Protein Pharmaceuticals, Fait A: Chemical and Physical Pathways of Protein Degradation Plenum Press, i99i. $79.50 (xxviii + 434 pages} ISBN 0 306 44152 7 Tim J. Ahem and Mark C. Manning (eds) Stabilitu of Protein Pharmaceuticals. Part 8: In Vi;o ‘Pathways of Degradation and Strategies for Protein Stabilization Plenum Press,-199i. $65.00 (xxvi + 327 pages) ISBN 0306441535 A. A. Boufton, G. B. Baker and P. H. Wu (eds) Animal Models of Drug Addiction Humana Press, 1992. E104.00 (xxii + 436 pages) ISBN 0 89603 217 5 F. Brown et al. Vaccine Design John Wiley, 1993. E19.50 (130 pages) ISBN 0 47193727 4 Ciba Foundation Symposium CorticotropinReteasing &&or John Wiley, 1993. ~45.00 (x + 357 pages) ISBN 0 47193448 8 William F. Calmers and Claes Wahiestedt (eds) The Biology of Neuropeptide Y and Related Peptides Humana Press, 1993. $119.50 (xvi + 564 pages) ISBN 0 89603 2418 Detfef Gabel and Ray Moss feds) Boron Neafron fupture ~erapy: Towards CZinical Triafs of GIioma Treatment Plenum Press, 1992. $79.50 (ix + 279 pages) ISBN 0 306 44350 3 G. Gregoriadis, A. T. Florence and G. Poste teds) Targeting of Drugs 3: The Challenge of Peptides and Proteins Plenum Press, 1992. $59.50 (viii + 129 pages) ISBN 0 306 44400 3
JAMES M. VEAL Gfaxo Research Instifute, Research Triangle Park, NC 27709, USA.
T-L. Ho (ed.) Heterotytic Fragment&ion of Organic Molecules John Wiley, 1993. E67.00 (ix + 326 pages) ISBN 0 47158101 1 C. L-H. Huane lntramembrane Charge Movements in St&fed Muscle Oxford &iversity Press, 1993. E45.00 (x + 292 pages) ISBN 0 19 857749 4 Lester Packer led,) Methods in Enzymology, Volume 214 Carotenoids, Part B: Metabolism, Genetics and Biosynthesis Academic Press, 1993. E57.00 (xxvii + 468 pages) ISBN 0 12 182115 3 D. S. Pathak,
A. Escovitz and S. Kucukarstan (eds) prorno~~o~ of P~~~~~eu~c~l~ Pharmaceutical Products Press, 1992. $32.95 (167 pages) ISBN 156024 383 X H. Smith and R. M. Cook Ieds) The Handbook of Immunophar:w&og~: Immunopharmacology of Eosrrzophils Academic Press, 1993. f40.00 (xii + 250 pages) ISBN 0 12 652270 7 T. W. Stone (ed.) Acetytcho~j~e, Sigma Receptors, CCK and Eicosanoids, Nt-wofoxins Taylor & Francis, 1993. E45.00 (266 pages) ISBN 0 7484 0063 X M. Tarr and F. Samson (eds) Oxygen Free Radicals in Tissue Damage Birkhluser, 1993. DM188.00 (x + 295 pages) ISBN 3 7643 3609 9
Beverly A. Teicher
(ed.) Drug Resistance in Oncology Marcel Dekker, 1993. $195.00 (xii + 654 pages) ISBN 0 8247 8804 4 B. Testa, W. Fuhrer, E. Kyburz and R. Giger (eds) Perspectives in Medicinal Chemist y VCH, 1993. DM225.00 (xii + 644 pages) ISBN 3 527 28486 9
A synaptic dimension Ion Channels
Vol. 3
edited by Toshio Narahashi, Plenum Press, 1992. $75.00 (xv + 350 pages) ISBN 0 306 44166 7 This, the third volume of Ion Channels, further establishes the reputation of the series by giving a broad perspective, with the authors providing a detailed and personal view of their subjects. The book concentrates on the regulation of ligand-gated ion channels and aspects of their kinetics, but there are also chapters on voltage-sensitive Ca2+ channels, developmental aspects of K+ currents and neurogenetic studies of voltage-gated channels. This is complimented by chapters on axon terminal excitability and epilepsy and an elegant chapter on neural correlates of memory storage in Hermissenda, which helps link some of the more mechanistic strands in the book. The stated aim is to inform the general reader and specialist alike of new developments and current progress in the field. The field is immense, potentially extending well outside the traditional boundaries of ‘excitable tissues’ no doubt this is why such an uninformative title was originally selected. However, this volume is well and truly anchored in the nervous system. While there appears to have been some attempt to avoid a thematic approach, the topics are of particular relevance to synaptic transmission and mechanisms of plasticity. Although modulation of voltagegated currents in general and Ca2+ currents in particular will regulate transmitter release, most of the work presented here concerns modulation of postsynaptic receptors through phosphorylation by second cascades. messenger Taking the nicotinic acetylcholine receptor as the prototypical ligandgated channel, functional regulation by G proteins and kinases are examined. The general application of such regulation is implied by reference to GABAA receptor function, In addition, there is an interesting article on the gating of GABA* receptor ion channels, which includes data on regulation by barbiturates, benzodiazepines and steroids at the single channel level.
385 In the recent past, the development of methods enabling submillisecond control of agonist application has permitted analysis of channel activation and desensitization by glutamate receptors to be related to the timecourse of synaptic transmission. Using one such method, Dude], Franke and Hatt bring together work from vertebrates and invertebrates in an informative discussion of activation and fast desensitization of ligand-gated channels. On the down side, some of the molecular biology of K+ channels has dated quickly and the quanta1 data have been over-interpreted in the chapter on synaptic transmission mediated by amino acids.
But these are minor gripes - the great strength of this volume is the breadth of its outlook in bringing together related issues from voltage-gated to ligandgated receptors in both vertebrate and invertebrate preparations. As Toshio Narahashi reminds us in the preface, many therapeutic drugs exert their effects through interactions with ion channels. So for those of you interested in a synaptic dimension to your pharmacology, I can thoroughly recommend this book as an invaluable resource. I. D. FORSYTHE
Acid test
The text is a companion to Computer Aided Drxg Design and, as a result, the role of molecular modelling in drug design is emphasized throughout the book. However, there are also substantial sections devoted to X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy studies. The volume therefore mainly deals with the structural specifics of nucleic acid interactions, and encompasses both theoretical and experimental studies. The book is divided into two main sections, methods and applications, although the division seems somewhat artificial. In the methods section, chapters deal with the use of X-ray crystalNMR spectroscopy, lography, structure-activity quantitative relationships (QSAR), computational chemistry and footprinting techniques. These chapters contain introductory discussions and are illustrated by experimental cr theoretical data. The applications section presents more examples of nucleic acid interactions without the descriptions of the experimental methods. A wide range of nucleic acid complexes are discussed. These include a number of small-molecule intercalation and minorgroove complexes that bind both noncovalently. covalently and pyrrolo(l,4-benzoLexitropsins, diazepines, enediyne antibiotics, quinolones, anthraquinones and quinolines are all reviewed in avaiiable The some detail. crystalacid protein-nucleic
Nucleic Acid Targeted Design
Drug
edited by C. L. Fropst and Thomas !. Perun. Marcel Dekker, 1992. $265.00 (xiii + 644 pages) ISBN 0 8247 8662 9 The design, synthesis and characterization of molecules that interact with nucleic acids is currently an area of intense research. Nucleic acids have iong been a target for drug design as, for example, in the development of anthracyclines. However, in the past decade, substantial information has been obtained on the structural basis of ligand-nucleic acid, protein-nucleic acid and nucleic acid-nucleic acid interactions. Notable advances have also been made in the biological characterization of ternary complexes between drug molecules, nucleic acids and various enzymes and topoisomerases such as polymerases. Chemical advances have also fostered the development of modified nucleic acids that are capable of binding to complementary nucleic acid sequences with high affinity and specificity. These structural, biological and chemical advances have all focused new attention on nucleic acids as a target for drug design. Nucleic Acid Targeted Drug Design provides both an overview of the current understanding of nucleic acids as a target for drug design and a detailed analysis of certain nucleic acid-ligand and nucleic acid-protein interactions.
Department
of Physiology. Box 138,
Leicester, PO LEI 9HN.
University of Leicesfer, UK
TiPS - Ocfober 1993 [Vol. 141 data are also discussed extensively. Finally, ribozyme and antisense-antigene drug-design with strategies are discussed relevant examples. The book is a fairly comprehensive survey of the field of nucleic acid drug design, but one area of weakness is the lack of a focused discussion on the role of solvation-desolvation phenomena in the binding of ligands to nucleic acids. While the subject is mentioned at various points in the book, a specific analysis of sol-
lographic
New edition Annual Review of Pharmacology and Toxicology, Volume 33, 1993 edited by Arthur K. Cho, Terrence F. Elaschke, Horace N. ioh and jnmes L. Way, Annual Reviews, 2993. $44.00 in USA and Canada {~~9.#0 elsewhere) fvi f 696 pages) 1SBN 0 8243 01330 The quest for a cure, Gertrude B. Elion; Adventures in autopharmacology: a biographic view with digressions into other matters, M. 1. Rand; Calmodulin in neurotransmitter and hormone action, Margaret E. Gnegy; Pharmacology of the endothelium in ischemiareperfusion and circulatory shock, Allan M. Lefer and David I. Lefer; Antiinflammato~ peptide agonists, Edward T. Wei and golly A. Thomas; GABAB receptor pharmacology, Norman G. Bowery; HIV drug resistance, Douglas D. Richman; New antidepressants, Leo E. Holfister and lames L. C~aghorn; Recent studies on the structure and function of multisubstrate flavin-containing monooxygenases, D. M. Ziegler; Covalent modifications of Gproteins, Bernard Kwok-Keung rang and Harvey K. Yamane; Pharmacologic and therapeutic application of a2-adrenoceptor sL;btypes, Robert R. Ruffolo Jr, Andrew J. Nichols, jeffrey M. Stadel and 1. Paul Hieble; Molecular diversity of the dopamine receptors, Olivier Civelli, fames R. B~n~ow and David K. Grandy; Neuropeptide Y-related peptides and their receptors - are the receptors potential therapeutic drug targets?, Clazs Wahlestedt and Donald I. Reis; Effects of opioids on the hypothalam~pituita~-
and the corresponding hydrophobic effects would have been useful, given their critical role in both nucleic acid structure and interactions of nucleic acids with ligands. Another controversial area that could have been treated in more depth is the relative importance of electrostatic versus dispersion forces in governing the affinity and specificity of nucleic acid-l&and interactions. Both the above points are of particular interest to computational chemists involved in the
field of nucleic acid research. the book is recOverall, ommended both as an instructional text and as a reference; it is a good update of our current knowledge and understanding of nucleic acids as a target for drug design. In general, the text is clear, and the wealth of structural information summarized and discussed makes this worthwhile reading.
adrenal axis, Robert N. Pechnick; Respiratory tract uptake of inhalants and metabolism of xenobiotics, Alan R. Dahl and J. L. Lewis; Childhood lead poisoning and its treatment, Carol R. Angle; Renal toxicity of non-steroidal ~ti-inflammato~ drugs, M. D. Murray and D. Craig Brater; of Parkinson’s Pharmacology disease therapy: an update, Irwin J. Kopin; Cardiovascular toxicity of anabolic steroids, Robin W. Rockhold; Prodrugs of peptides and
proteins for improved formulation and delivery, Reza Oliyai and Valentine 1. Stella; Molecular and ionic mimicry of toxic metals, Clarkson; Gene Thomas W. therapy: concepts, current trials, and future directions, Paul Tolstoshev; The pharmacology of ATP-sensitive potassium channels, GilIian Edwards and A. H. Amphetamine: effects Weston; on catecholamine systems and behavior, Lewis S. Seiden, Karen E. Sabol and George A. Ricaurte.
vation
Books received Tim 1. Ahem and Mark C. Mannine (eds) Sfabiiify of Protein Pharmaceuticals, Fait A: Chemical and Physical Pathways of Protein Degradation Plenum Press, i99i. $79.50 (xxviii + 434 pages} ISBN 0 306 44152 7 Tim J. Ahem and Mark C. Manning (eds) Stabilitu of Protein Pharmaceuticals. Part 8: In Vi;o ‘Pathways of Degradation and Strategies for Protein Stabilization Plenum Press,-199i. $65.00 (xxvi + 327 pages) ISBN 0306441535 A. A. Boufton, G. B. Baker and P. H. Wu (eds) Animal Models of Drug Addiction Humana Press, 1992. E104.00 (xxii + 436 pages) ISBN 0 89603 217 5 F. Brown et al. Vaccine Design John Wiley, 1993. E19.50 (130 pages) ISBN 0 47193727 4 Ciba Foundation Symposium CorticotropinReteasing &&or John Wiley, 1993. ~45.00 (x + 357 pages) ISBN 0 47193448 8 William F. Calmers and Claes Wahiestedt (eds) The Biology of Neuropeptide Y and Related Peptides Humana Press, 1993. $119.50 (xvi + 564 pages) ISBN 0 89603 2418 Detfef Gabel and Ray Moss feds) Boron Neafron fupture ~erapy: Towards CZinical Triafs of GIioma Treatment Plenum Press, 1992. $79.50 (ix + 279 pages) ISBN 0 306 44350 3 G. Gregoriadis, A. T. Florence and G. Poste teds) Targeting of Drugs 3: The Challenge of Peptides and Proteins Plenum Press, 1992. $59.50 (viii + 129 pages) ISBN 0 306 44400 3
JAMES M. VEAL Gfaxo Research Instifute, Research Triangle Park, NC 27709, USA.
T-L. Ho (ed.) Heterotytic Fragment&ion of Organic Molecules John Wiley, 1993. E67.00 (ix + 326 pages) ISBN 0 47158101 1 C. L-H. Huane lntramembrane Charge Movements in St&fed Muscle Oxford &iversity Press, 1993. E45.00 (x + 292 pages) ISBN 0 19 857749 4 Lester Packer led,) Methods in Enzymology, Volume 214 Carotenoids, Part B: Metabolism, Genetics and Biosynthesis Academic Press, 1993. E57.00 (xxvii + 468 pages) ISBN 0 12 182115 3 D. S. Pathak,
A. Escovitz and S. Kucukarstan (eds) prorno~~o~ of P~~~~~eu~c~l~ Pharmaceutical Products Press, 1992. $32.95 (167 pages) ISBN 156024 383 X H. Smith and R. M. Cook Ieds) The Handbook of Immunophar:w&og~: Immunopharmacology of Eosrrzophils Academic Press, 1993. f40.00 (xii + 250 pages) ISBN 0 12 652270 7 T. W. Stone (ed.) Acetytcho~j~e, Sigma Receptors, CCK and Eicosanoids, Nt-wofoxins Taylor & Francis, 1993. E45.00 (266 pages) ISBN 0 7484 0063 X M. Tarr and F. Samson (eds) Oxygen Free Radicals in Tissue Damage Birkhluser, 1993. DM188.00 (x + 295 pages) ISBN 3 7643 3609 9
Beverly A. Teicher
(ed.) Drug Resistance in Oncology Marcel Dekker, 1993. $195.00 (xii + 654 pages) ISBN 0 8247 8804 4 B. Testa, W. Fuhrer, E. Kyburz and R. Giger (eds) Perspectives in Medicinal Chemist y VCH, 1993. DM225.00 (xii + 644 pages) ISBN 3 527 28486 9