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Folyl and Antifolyl Polyglutamates

  • Book
  • © 1983

Overview

Editors:
  1. I. David Goldman

    1. Medical College of Virginia, Virginia Commonwealth University, Richmond, USA

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  2. Bruce A. Chabner

    1. National Cancer Institute, Bethesda, USA

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    You can also search for this editor in PubMed   Google Scholar

  3. Joseph R. Bertino

    1. Yale University School of Medicine, New Haven, USA

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Part of the book series: Advances in Experimental Medicine and Biology (AEMB, volume 163)

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Table of contents (28 chapters)

  1. Front Matter

    Pages i-x
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  2. Folylpolyglutamates: Interaction with Folate Dependent Enzymes

    1. Molecular Basis for the Interaction of Polyglutamates of Folic Acid and its Analogs with Dihydrofolate Reductase

      • Raymond L. Blakley, Anna Crane, Lennie Cocco, Charles M. Baugh
      Pages 1-18

    2. Interaction of Tetrahydropteroylpolyglutamates with Two Folate-Dependent Multifunctional Enzymes

      • Robert E. MacKenzie, Charles M. Baugh
      Pages 19-34

    3. The Role of Folylpolyglutamates in the Regulation of Folate Metabolism

      • Rowena G. Matthews, Jonathan Ross, Charles M. Baugh, Janine D. Cook, Leodis Davis
      Pages 35-44

    4. Studies on Identifying the Binding Sites of Folate and its Derivatives in Lactobacillus Casei Thymidylate Synthase

      • Frank Maley, Gladys F. Maley
      Pages 45-63

    5. The Interaction of Pteroylpolyglutamates with Calf Thymus Thymidylate Synthase

      • Chandra M. Dwivedi, Roy L. Kisliuk, Charles M. Baugh
      Pages 65-70

    6. An Hypothesis on the Role of Pteroylpolyglutamate Derivatives as Coenzymes

      • Roy L. Kisliuk, Yvette Gaumont
      Pages 71-74

    7. Chemical Synthesis of Folylpolyglutamates, their Reduction to Tetrahydro Derivatives, and their Activity with Yeast C1-THF Synthase

      • Jesse C. Rabinowitz
      Pages 75-83

    8. Thymidylate Synthase, Dihydrofolate Reductase, Folyl Binder, 10-Formyl-H4PteGlu Synthetase, 5,10-Methenyl-H4PteGlu Cyclohydrolase and 5,10-Methylene-H4PteGlu Dehydrogenase Derived from Cells of Human Origin

      • Yung-chi Cheng, Barbara A. Domin, Dennis Conrad
      Pages 85-94

  5. Characteristics of the Formation and Disposition of Antifolate Polyglutamates in Mammalian Cells and their Potential Relevance to Drug Action

    1. Characteristics of the Accumulation of Methotrexate Polyglutamate Derivatives in Ehrlich Ascites Tumor Cells and Isolated Rat Hepatocytes

      • David W. Fry, David A. Gewirtz, Jack C. Yalowich, I. David Goldman
      Pages 215-234

    2. Studies of Formation and Efflux of Methotrexate Polyglutamates with Cultured Hepatic Cells

      • John Galivan, Malgorzata Balinska
      Pages 235-246

    3. Synthesis, Binding and Intracellular Retention of Methotrexate Polyglutamates by Cultured Human Breast Cancer Cells

      • Richard L. Schilsky, Jacques Jolivet, Brenda D. Bailey, Bruce A. Chabner
      Pages 247-257
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Keywords

About this book

The role of folylpolyglutamates in biosynthetic processes has gained increasing importance with the recognition that these com­ pounds are not only the forms of folate co-factors that accumulate within cells, but, in addition, are the preferred substrates for folate dependent reactions in eukaryotic cells. More recently attention has turned to the potential importance of the polyglutamyl derivatives of methotrexate that have been detected in normal and malignant cells both in vitro and in vivo. The biochemical trans­ formation of this important chemotherapeutic agent is of particular significance since polyglutamyl derivatives of methotrexate are not only potent inhibitors of the target enzyme, but have quite different cellular pharmacokinetics than the parent monoglutamate. Hence, nearly three and a half decades after 4-aminoantifolates were first applied clinically in the treatment of human neoplasms, we have begun to appreciate a new dimension in antifolate pharmaco­ logy which may have profound implications for our understanding of the mechanism of the cytotoxicity and selectivity of this class of agents. With the development of highly sensitive methodology for the rapid detection of folyl and antifolyl polyglutamates, it is now possible to define in depth the intracellular transformation of these agents and their role in determining antifolate action against normal and malignant cells. This information will very likely influence how regimens with methotrexate and related antifolates will be further developed and employed clinically.

Editors and Affiliations

  • Medical College of Virginia, Virginia Commonwealth University, Richmond, USA

    I. David Goldman

  • National Cancer Institute, Bethesda, USA

    Bruce A. Chabner

  • Yale University School of Medicine, New Haven, USA

    Joseph R. Bertino

Bibliographic Information

  • Book Title: Folyl and Antifolyl Polyglutamates

  • Editors: I. David Goldman, Bruce A. Chabner, Joseph R. Bertino

  • Series Title: Advances in Experimental Medicine and Biology

  • DOI: https://doi.org/10.1007/978-1-4757-5241-0

  • Publisher: Springer New York, NY

  • eBook Packages: Springer Book Archive

  • Copyright Information: The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature 1983

  • Softcover ISBN: 978-1-4757-5243-4Published: 15 May 2013

  • eBook ISBN: 978-1-4757-5241-0Published: 01 December 2013

  • Series ISSN: 0065-2598

  • Series E-ISSN: 2214-8019

  • Edition Number: 1

  • Number of Pages: X, 425

  • Topics: Pharmacology/Toxicology

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