H K Majumder

Drug Targets in Kinetoplastid Parasites - Advances in Experimental Medicine and Biology H K Majumder 2008 edition

Marc Notes: Includes bibliographical references and index. Table of Contents: 1. Arsenite Resistance in Leishmania and Possible Drug Targets / Gaganmeet Singh, K. G. Jayanarayan, Chinmoy S. Dey -- Abstract -- Introduction -- Arsenite Resistance in Leishmania -- Potential Drug Targets -- Conclusion -- 2. Unique Characteristics of the Kinetoplast DNA Replication Machinery Provide Potential Drug Targets in Trypanosomatids / Dotan Sela, Neta Milman, Irit Kapeller, Aviad Zick, Rachel Bezalel, Nurit Yaffe, Joseph Shlomai -- Reevaluating the Kinetoplast as a Potential Target for Anti-Trypanosomal Drugs -- The kDNA Network and Its Monomeric Components -- Unique Characteristics of the kDNA Replication System -- Replication of Free kDNA Minicircles and Catenated Maxicircles -- Regulation of kDNA Replication -- Concluding Remarks -- 3. Drugs and Transporters in Kinetoplastid Protozoa / Scott M. Landfear -- Abstract -- Introduction -- Roles of Membrane Transport Proteins among the Kinetoplastida -- Leishmania Glucose Transporters -- Leishmania Purine Transporters -- 4. Selective Lead Compounds Against Kinetoplastid Tubulin / R. E. Morgan, K. A. Werbovetz -- Abstract -- Introduction -- Oryzalin as a Lead Compound against Kinetoplastid Tubulin -- Aromatic Thiocyanates as Lead Compounds -- Generating New Leads -- Conclusion -- 5. Fishing for Anti-Leishmania Drugs: Principles and Problems / Emanuela Handman, Lukasz Kedzierski, Alessandro D. Uboldi, James W. Goding -- Abstract -- Introduction -- The Disease Burden of Leishmaniasis -- Transmission and Epidemiology -- Disease Manifestations -- Management and Control of Leishmaniasis -- The Impact of New Technologies on Drug Discovery -- High Throughput Screening -- Structure-Based Drug Discovery -- Proteomics -- Monoclonal Antibodies -- Natural Products -- Target Selection and Validation -- Proteins and Metabolic Pathways Unique to the Parasite -- Proteins Essential for Parasite Survival and Virulence Factors -- Target Validation -- Concluding Remarks -- 6. Sterol 14-Demethylase Inhibitors for Trypanosoma Cruzi Infections / Frederick S. Buckner -- Abstract -- Introduction -- Chagas Disease -- Drug Development for Changes Disease -- Sterol Biosynthesis-Overview -- Sterol 14-Demethylase (CYP51) and Azole Inhibitors -- Sterols of T. cruzi -- Activity of Azole Compounds against T. cruzi -- The Development Status of Sterol 14-Demethylase Inhibitors -- Can a Better Sterol 14-Demethylase Inhibitor Be Developed against T. cruzi? -- Summary -- 7. Histone Deacetylases / David Horn -- Abstract -- Introduction -- The Deacetylases -- The Inhibitors -- Current Research -- Summary -- 8. Targeting Glycoproteins or Glycolipids and their Metabolic Pathways for Antiparasite Therapy / Sumi Mukhopadhyay nee Bandyopadhyay, Chitra Mandal -- Abstract -- An Introduction to the Kinetoplastid Parasites -- Trypanosomiasis -- Leishmaniasis -- Why Target Glycoproteins and Glycolipids? -- Glycoconjugates of Trypanosomes -- Biological Relevance of Glycoconjugates in Trypanosomiasis -- Targeting VSG Epitopes -- Targeting Mucin Glycoproteins -- Lactose Derivatives Are Inhibitors of Trans-Sialidase Present in the Mucins -- Glycoconjugate Biosynthetic Machinery in Trypanosome -- Targeting Enzymes of the Biosynthetic Pathway -- Glycoconjugates of Leishmania -- Biological Relevance -- Development of Anti-Leishmanials by Targeting -- gp63 Producing Enzymes -- Galactofuranose on LPG -- Sialoglycans -- Other Glyoconjugates -- PPG -- Glycosylphosphatidylinositol (GPI) Lipids -- Enzymes Producting Glycoproteins -- As Drug Carrier -- Perspective -- 9. DNA Topoisomerases of Leishmania: The Potential Targets for Anti-Leishmanial Therapy / Benu Brata Das, Agneyo Ganguly, Hemanta K. Majumder -- Abstract -- Introduction -- DNA Topoisomerases: The Wonder Enzyme -- Classification of DNA Topoisomerases -- Topoisomerases of Kinetoplastid Parasites -- Topoisomerases as Therapeutic Targets -- Conclusion -- 10. Antiparasitic Chemotherapy: Tinkering with the Purine Salvage Pathway / Alok Kumar Datta, Rupak Datta, Banibrata Sen -- Summary -- General Strategies for Development and Characterisation of Drug Targets in Trypanosomatids -- Acquisition and Assimilation of Purines in L. donovani Promastigotes -- Purine Metabolism in L. donovani Amastigotes -- Purine Salvage Enzymes as Targets for Structure-Based Inhibitor Design -- Prospects of Adenosine Kinase (AdK) as the Drug Target -- General Biochemical Properties of the L. donovani AdK -- Structure of AdK from Different Sources -- Sequence Characteristics of LdAdK Gene and Homology Model-Based Structural Analysis of the Protein -- Identification of Potential Amino Acid Residues Involved in Catalysis -- Mechanism of Ado Binding -- Mechanism of Phosphate Transfer -- Product-Mediated Enzyme Regulation -- Conclusions and Perspectives -- 11. Searching The Tritryp Genomes for Drug Targets / Peter J. Myler -- Abstract -- Tritryp Genome Content -- Computational Approaches for Drug Target Selection -- Databases of Tritrype Metabolism -- Identification of Metabolic Choke-Points -- Searching for Parasite Orthologues of Known Drug Targets -- Matching Drug-Like Chemicals to Parasite Proteins -- Conclusion -- 12. Purine and Pyrimidine Metabolism in Leishmania / Nicola S. Carter, Phillip Yates, Cassandra S. Arendt, Jan M. Biotz, Buddy Ullman -- Abstract -- Nomenclature -- Purine Metabolism -- Purine Transport in Leishmania -- Purine Transporters as Drug Targets in Leishmania -- Structure-Function Studies on Purine Transporters -- Purine Salvage Enzymes of Leishmania -- Purine Salvage Enzymes as Drug Targets in Leishmania -- The Compartmentalization of Purine Salvage in Leishmania -- Pyrimidine Metabolism -- Pyrimidine Biosynthesis in Leishmania -- Pyrimidine Salvage and Nucleotide Synthesis in Leishmania -- The Pyrimidine Pathway as a Drug Target in Leishmania -- Summary -- Index. Publisher Marketing: If viewed globally, the parasitic diseases pose an increasing threat to human health and welfare. The diseases caused by kinetoplastid protozoan parasites like Leishmania and Trypanosoma continue as a cause of suffering for many millions of people in both tropical and subtropical regions of the world. Leishmania species are found throughout Latin America, Africa and Asia. Trypanosoma cruzi that cause Chagas disease is endemic in Latin America, while members of Trypanosoma brucei group are found in sub-Saharan Africa. Although the past two decades has witnessed commendable research efforts and technical advances in our understanding of the biochemistry, molecular and cell biology of these pathogens, the dreaded protozoal diseases caused by these organisms threaten mankind. Therapeutic tools for the treatment of most parasitic diseases are extremely limited. The development of parasites resistant to many of the available drugs is also responsible for the depressing picture of disease persistence and death. Development of commercially available vaccines is still far from reality, though research and trial programs continue.