Biological Methylation and Drug Design

1. Front Matter

   Pages i-xxi

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2. Protein and Phospholipid Methylations

   1. Front Matter

      Pages 1-1

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   2. Protein Methylation at Abnormal Aspartyl Residues

      • Steven Clarke

      Pages 3-14

   3. Enzymology of Protein Methylation: Recent Development

      • Woon Ki Paik, Sangduk Kim, Hyang Woo Lee

      Pages 15-23

   4. Is There a Function for Protein Carboxylmethylation in the Nervous System?

      • Melvin L. Billingsley, Randall L. Kincaid, Marina E. Wolf, Robert H. Roth, Walter Lovenberg, Carey D. Balaban et al.

      Pages 25-41

   5. Methyl-Accepting Chemotaxis Proteins in Bacteria

      • Gerald L. Hazelbauer, John Bollinger, Chankyu Park, Dawn Nowlin, Maqsudul Alam

      Pages 43-53

   6. Biochemistry of Methylated Phospholipids

      • Jon Bremer, Kaare Norum, Pål Bjørnstad

      Pages 55-66

   7. Phospholipid Methylation and Cellular Differentiation

      • Fusao Hirata, Masakazu Hatanaka, Yuji Wano, Keiichi Matsuda

      Pages 67-74

   8. Methylation of Phosphatidylethanolamine: Enzyme Characterization, Regulation and Physiological Function

      • Dennis E. Vance, Neale Ridgway

      Pages 75-88

   9. Regulation of Phospholipid Methylation by Reversible Phosphorylation

      • I. Varela, M. Pajares, I. Merida, M. Villalba, C. Cabrero, P. Ortiz et al.

      Pages 89-99

   10. Brain Phosphatidylcholine Pools as Possible Sources of Free Choline for Acetylcholine Synthesis

       • M. Lakher, R. J. Wurtman, J. Blusztajn, P. Holbrook, J-C. Maire, C. Mauron et al.

       Pages 101-110

3. Nucleic Acid Methylations

   1. Front Matter

      Pages 111-111

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   2. DNA Methylation: Overview and Prospectives

      • Thomas W. Sneider

      Pages 113-126

   3. Tissue Specific DNA Methylation Patterns: Biochemistry of Formation and Possible Role

      • Aharon Razin

      Pages 127-137

   4. Regulation of Gene Expression by Site-Specific Promoter Methylation

      • Walter Doerfler, Klaus-Dieter Langner, Dagmar Knebel, Ulrike Weyer

      Pages 139-150

   5. Carcinogenesis and DNA Hypomethylation in Methyl-Deficient Animals

      • Lionel A. Poirier, Mary J. Wilson, Narayan Shivapurkar

      Pages 151-161

   6. The Role of Coenzymes and tRNA Modifications in Metabolic Control of Gene Expression

      • H. Kersten

      Pages 163-174

   7. Relationship Between Methylation and Maturation of Ribosomal RNA in Prokaryotic and Eukaryotic Cells

      • Jean-Hervée Alix

      Pages 175-187

   8. Distribution of m6A in mRNA and its Possible Biological Role

      • F. Rottman, P. Narayan, R. Goodwin, S. Camper, Y. Yao, S. Horowitz et al.

      Pages 189-200

4. Regulation of S-Adenosylmethionine, S-Adenosylhomocysteine, and Methylthioadenosine Metabolism

   1. Front Matter

      Pages 201-201

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This book has been developed from its earlier and far less formal presentment as the proceedings of a symposium entitled The Biochemistry of S-Adenosylmethionine as a Basis for Drug Design that was held at the Solstrand Fjord Hotel in Bergen, Norway on June 30-July 4, 1985. The purpose of the symposium was to bring together scientists from various disciplines (biochemistry, pharmacology, virology, immunology, chemistry, medicine, and so on) to discuss the recent advances that have been made in our understanding of the biological roles of S­ adenosylmethionine (AdoMet) and to discuss the feasibility of utilizing AdoMet-dependent enzymes as targets for drug design. Thus the information provided herein will be of value not only to basic scientists involved in elucidating the role of AdoMet in biology, but also to medicinal chemists who are using this basic knowledge in the process of drug design. The volume should also be of interest to pharmacologists and clinicians involved in biological evaluation of potential therapeutic agents arising from the efforts of the biochemists and medicinal chemists. Each plenary speaker at the symposium was requested to submit a chapter reviewing recent contributions of their discipline to our base of knowledge about the biological role of AdoMet. Topics covered in this volume include protein and phospholipid methylations (Section A), nucleic acid methyl­ ations (Section B), the regulation of AdoMet, S-adenosylhomocysteine, and methylthioadenosine metabolism (Section C), clinical aspects of AdoMet (Section D), and the design, synthesis, and biological evaluation of trans­ methylation inhibitors (Section E).

• Coenzym
• DNA
• RNA
• base
• biochemistry
• enzymes
• ethanol
• gene expression
• metabolism

• Pharmaceutical Chemistry Department, The University of Kansas, Lawrence, USA

  Ronald T. Borchardt

• NIADDK, National Institutes of Health, Bethesda, USA

  Cyrus R. Creveling

• Department of Pharmacology, University of Bergen, Bergen, Norway

  Per Magne Ueland

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