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The design of synthetic inhibitors of thrombin
Gen. Pharmac. Vol. 25, No. 8, pp. 1741-1742, 1994
Elsevier Science Ltd. Printed in Great Britain
Pergamon
BOOK REVIEWS Biochemistry of Zinc---A. S. Prasad. 303 pp. 1993. Plenum Press. New York. $79.50. Zinc metalloenzymes catalyse more than 50 biochemical reactions (carbonic, anhydrase, carboxypeptidase, alcohol dehydrogenase, transferase, hydrolases, lyases, ligases, thermolysin, aldolases, etc). More than 200 ealytically active zinc metalloproteins have been identified. Zinc plays an important role in gene expression. It is involved in the recognition of DNA via the zinc finger. Zinc deficiency affects the development of the neural tube and can lead to agenesis, dysmorphogenesis of the CNS and hydrocephalus. Zinc deficiency has been linked to immune deficiency disorders and growth retardation in children and adolescents. It can lead to anergy; decreased NK cell activity; reduced IL-1 and IL-2 production; decreased lymphocyte production; and thymic atrophy; Biochemistry of Nickel---R. P. Hausinger. 280 pp. 1993. Plenum Press. New York. $79.50. Nickel is a coordination element that is present in some bacterial and plant ureases, hydrogenases, carbon monoxide dehydrogenase (used in carbon dioxide fixation under anaerobic conditions) and methyl coenzyme M reductase (used in anaerobic production of methane). Nickel is often present as an air pollutant especially in the vicinity of nickel works as at Sudbury, Ontario. Nickel is present in many foods and most is eliminated in the faeces. Some is absorbed by cells in the small intestine (160-300 #g/day). Additional small amounts (0.16#g/day) are taken up by pulmonary cells after inhalation. The nickel is taken up by serum albumin and is accumulated in the kidneys, which are the major route for elimination of nickel via the urine. It is not clear if nickel is an essential or even a beneficial trace element but low concentrations of nickel appear to facilitate optimal growth in rats, lambs and goats. It is possible that nickel is essential for many of the bacteria present in the human gut. Nickel can also form a stable complex with C convertase of human complement, with calcineurin, and can activate phosphatidyl serine biosynthesis. Nickel is a leading cause of contact dermatitis with a prevalence of 7-10% in women and 1-2% in men. High levels of nickel can lead to renal damage, hepatic toxicity, lung damage, pulmonary and nasal cancers. Modern Medicinal Chemistry--J. B. Taylor and P. D. Kennewell. 290pp. 1993. Ellis Horwood/Simon and Schuster. New York.
mixture of the crude extract. This volume deals with the methods used in the purification of macromolecules based on molecular interactions, i.e. affinity related techniques. It deals with affinity chromatography with biological ligands; with biomimetic ligands; immuno-affinity separation; molecular imprinted polymers; extraction of toxic substances directly from whole blood; heparin removing and sensing devices; affinity precipitation; monosized magnetic beads used in affinity separation of nucleic acids; affinity ultraflltration for protein purification; reversed mieelles for protein purification. The Sterie Factor in Medicinal Chemistry; Dissymetric Probes of Pharmacological Receptors---A. F. Casy. 570 pp. 1993. Plenum Press. New York. $125. In many drugs only one of a chemical antipodal-pair will form a good threepoint fit onto a receptor. This can often be revealed by SAR steroehemical analysis. This text deals with conformation effects; methodology; pharmacokinetics including the use of racemic mixtures in therapy; adrenergic ligands; adrenoreceptor antagonists; dopamine agonists and antagonists; cholinergic agonists; muscarinic antagonists; nicotinic cholinergic receptors, including neuromuscular blocking agents; histamine receptors; 5HT ligands; opioid ligands; The book gives a very thorough, detailed, but readable account of an important subject.
The Design of Synthetic Inhibitorsof Thrombin--Edited by G. Claeson, M. F. Scully, V. Kakkar and J. Deadman. 246 pp. 1993. Plenum Press. New York. $75. The two main drugs used for the prevention and control of thrombosis are heparin and coumarin and these were developed over 50 years ago. The crystal structure of alpha thrombin was determined in 1989 and the knowledge that alpha thrombin was inhibited by o-Phe-Pro-Arg chlormethyl ketone facilitated the understanding of the interatomic interactions between this enzyme and fibrinogen and other substrates. The main topics of this book are; the structural features of the interaction of thrombin with substrates and inhibitors; synthetic inhibitors [TAMe, peptide boronic inhibitors, peptide fluoroalkanes]; hirudin and its analogs; pharmacological and clinical considerations.
Ion Flux in Pulmonary Vascular Control--Edited by E. K. Weir, J. R. Hume and J. T. Reeves. 347 pp. 1993. Plenum Press. New York. $105.
This is a successor text to the authors' "Medicinal Chemistry" and includes the developments that have taken place over the last 11 years. It is very readable and covers the basic chemical and pharmaceutical material required by first and second year university students, and also gives emphasis to the design of new drugs, drug targeting and delivery systems, legislative issues, and modern techniques. Molecular Interactions in Binseparatiom--Edited by T. T. Ngo. 570 pp. 1993. Plenum Press. New York. $95. A major cost of producing protein-based therapeutic agents is associated with their purification from a complex
Potassium channel blockers and calcium channel blockers can help in regulating pulmonary vascular tone. This symposium volume deals with; pulmonary hypertension; electrophysiology of smooth muscle; calcium control (arterial smooth muscle, vascular smooth muscle, Na--Ca exchange, Ca-ATPases, fast Na and Ca currents); potassium channels (activated by Ca release from sarcoplasmic reticulum, ATP sensitive channels, effect of prostacyclin analogs); potassium channels and oxygen sensing (K channels modulated by hypoxia and redox status, Na gradient, K channels and regulation of Ca in pulmonary and mesenteric smooth muscle-effect of hypoxia); ion fluxes in vascular endothelial
1741
Elsevier Science Ltd. Printed in Great Britain
Pergamon
BOOK REVIEWS Biochemistry of Zinc---A. S. Prasad. 303 pp. 1993. Plenum Press. New York. $79.50. Zinc metalloenzymes catalyse more than 50 biochemical reactions (carbonic, anhydrase, carboxypeptidase, alcohol dehydrogenase, transferase, hydrolases, lyases, ligases, thermolysin, aldolases, etc). More than 200 ealytically active zinc metalloproteins have been identified. Zinc plays an important role in gene expression. It is involved in the recognition of DNA via the zinc finger. Zinc deficiency affects the development of the neural tube and can lead to agenesis, dysmorphogenesis of the CNS and hydrocephalus. Zinc deficiency has been linked to immune deficiency disorders and growth retardation in children and adolescents. It can lead to anergy; decreased NK cell activity; reduced IL-1 and IL-2 production; decreased lymphocyte production; and thymic atrophy; Biochemistry of Nickel---R. P. Hausinger. 280 pp. 1993. Plenum Press. New York. $79.50. Nickel is a coordination element that is present in some bacterial and plant ureases, hydrogenases, carbon monoxide dehydrogenase (used in carbon dioxide fixation under anaerobic conditions) and methyl coenzyme M reductase (used in anaerobic production of methane). Nickel is often present as an air pollutant especially in the vicinity of nickel works as at Sudbury, Ontario. Nickel is present in many foods and most is eliminated in the faeces. Some is absorbed by cells in the small intestine (160-300 #g/day). Additional small amounts (0.16#g/day) are taken up by pulmonary cells after inhalation. The nickel is taken up by serum albumin and is accumulated in the kidneys, which are the major route for elimination of nickel via the urine. It is not clear if nickel is an essential or even a beneficial trace element but low concentrations of nickel appear to facilitate optimal growth in rats, lambs and goats. It is possible that nickel is essential for many of the bacteria present in the human gut. Nickel can also form a stable complex with C convertase of human complement, with calcineurin, and can activate phosphatidyl serine biosynthesis. Nickel is a leading cause of contact dermatitis with a prevalence of 7-10% in women and 1-2% in men. High levels of nickel can lead to renal damage, hepatic toxicity, lung damage, pulmonary and nasal cancers. Modern Medicinal Chemistry--J. B. Taylor and P. D. Kennewell. 290pp. 1993. Ellis Horwood/Simon and Schuster. New York.
mixture of the crude extract. This volume deals with the methods used in the purification of macromolecules based on molecular interactions, i.e. affinity related techniques. It deals with affinity chromatography with biological ligands; with biomimetic ligands; immuno-affinity separation; molecular imprinted polymers; extraction of toxic substances directly from whole blood; heparin removing and sensing devices; affinity precipitation; monosized magnetic beads used in affinity separation of nucleic acids; affinity ultraflltration for protein purification; reversed mieelles for protein purification. The Sterie Factor in Medicinal Chemistry; Dissymetric Probes of Pharmacological Receptors---A. F. Casy. 570 pp. 1993. Plenum Press. New York. $125. In many drugs only one of a chemical antipodal-pair will form a good threepoint fit onto a receptor. This can often be revealed by SAR steroehemical analysis. This text deals with conformation effects; methodology; pharmacokinetics including the use of racemic mixtures in therapy; adrenergic ligands; adrenoreceptor antagonists; dopamine agonists and antagonists; cholinergic agonists; muscarinic antagonists; nicotinic cholinergic receptors, including neuromuscular blocking agents; histamine receptors; 5HT ligands; opioid ligands; The book gives a very thorough, detailed, but readable account of an important subject.
The Design of Synthetic Inhibitorsof Thrombin--Edited by G. Claeson, M. F. Scully, V. Kakkar and J. Deadman. 246 pp. 1993. Plenum Press. New York. $75. The two main drugs used for the prevention and control of thrombosis are heparin and coumarin and these were developed over 50 years ago. The crystal structure of alpha thrombin was determined in 1989 and the knowledge that alpha thrombin was inhibited by o-Phe-Pro-Arg chlormethyl ketone facilitated the understanding of the interatomic interactions between this enzyme and fibrinogen and other substrates. The main topics of this book are; the structural features of the interaction of thrombin with substrates and inhibitors; synthetic inhibitors [TAMe, peptide boronic inhibitors, peptide fluoroalkanes]; hirudin and its analogs; pharmacological and clinical considerations.
Ion Flux in Pulmonary Vascular Control--Edited by E. K. Weir, J. R. Hume and J. T. Reeves. 347 pp. 1993. Plenum Press. New York. $105.
This is a successor text to the authors' "Medicinal Chemistry" and includes the developments that have taken place over the last 11 years. It is very readable and covers the basic chemical and pharmaceutical material required by first and second year university students, and also gives emphasis to the design of new drugs, drug targeting and delivery systems, legislative issues, and modern techniques. Molecular Interactions in Binseparatiom--Edited by T. T. Ngo. 570 pp. 1993. Plenum Press. New York. $95. A major cost of producing protein-based therapeutic agents is associated with their purification from a complex
Potassium channel blockers and calcium channel blockers can help in regulating pulmonary vascular tone. This symposium volume deals with; pulmonary hypertension; electrophysiology of smooth muscle; calcium control (arterial smooth muscle, vascular smooth muscle, Na--Ca exchange, Ca-ATPases, fast Na and Ca currents); potassium channels (activated by Ca release from sarcoplasmic reticulum, ATP sensitive channels, effect of prostacyclin analogs); potassium channels and oxygen sensing (K channels modulated by hypoxia and redox status, Na gradient, K channels and regulation of Ca in pulmonary and mesenteric smooth muscle-effect of hypoxia); ion fluxes in vascular endothelial
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