The Impact of Protein Chemistry on the Biomedical Sciences

Contributors and Participants

Preface

Introduction: The Anfinsen Series

Christian Anfinsen and The National Institutes of Health

Part I. Research in Perspective


1. Historical Perspective of Biomedical Research

A. Baird Hastings


2. Basic Research as an Investment in the Nation's Future

I. Background

II. A Glimpse of Activities in the OSTP

III. Closing Remarks

References

Part II. Protein Chemistry


3. From Polypeptide Chemistry to Muscle Contraction

Text

References


4. Serum Albumin: Adventures of a Circulating Protein

I. Features of Albumin

II. Mode of Biosynthesis of Albumin

III. Nature of the Intracellular Albumin: Proalbumin

IV. Albumin in the Circulation

V. Fate of Albumin

VI. Conclusion

References


5. What Does Hydrogen Exchange Tell Us about Proteins?

I. The Hydrogen-Exchange Method

II. Interpretation of Exchange Rates

References


6. The Mechanism of Protein Folding

I. Equilibrium Ensembles of Protein Conformations

II. Information for Cooperative Folding

III. Linkage of Interatomic Interactions

IV. Determinant of the Ordered Structure

V. Dynamic Equilibrium of Folding and Unfolding

VI. Cytochrome c Fragment-Complementing System

VII. Energy Barrier for Unfolding

VIII. Concluding Remarks

References


7. Chemical Syntheses and Biological Activities of Cyclic Peptides

I. General Features of Microbial Peptides

II. Syntheses and Antibacterial Activities of Gramicidin S and Its Analogs

III. Syntheses and Necrotic Activities of AM Toxins and Their Analogs

References


8. Affinity Labeling: From Nuclease to Cells

I. Affinity Labeling

II. Affinity Labeling of Nuclease

III. Affinity Labeling of Antibodies

IV. Affinity Labeling of Ribosomes

V. Affinity Labeling of Hormone Carrier and Receptor Proteins

VI. Affinity Labeling of Cells

VII. Conclusions

References


9. Structural Bases of Biological Function: From Nucleases to Neurophysins

I. Heritage of the Observation of Spontaneous Self-Assembly

II. Semisynthesis as a Probe of the Sequence Code

III. Biosynthetic Origin of Peptides and Proteins

IV. Concluding Remarks

References


10. Staphylococcal Nuclease, a Calcium-Binding Protein: Path to the Vitamin K-Dependent Blood Coagulation Proteins

Text

References

Part III. Immunology


11. Molecular Evolution, Antibody Formation, and Embryogenesis

I. Molecular Evolution

II. Antibody Formation

III. Embryogenesis

IV. Status of the Embryogenesis Problem

References


12. The Combining Site of Antibodies: From the Protein to the Gene

I. Affinity Labeling of the Antibody Combining Site

II. Preparation of Fv Fragments

III. Model-Building Studies

IV. Structure and Diversity of Immunoglobulin VH Genes

V. Sequence of the 5' Noncoding and Leader Regions

VI. Sequence of VH Coding Region and the Recombination Signals

VII. Evolutionary Diversity of VH Genes

VIII. Immune VH Gene Repertoire Is Rich in Pseudogenes

IX. Conclusion

References


13. Protein Conformation and Biological Function: From Ribonuclease to Antigens and Antibodies

I. From Ribonuclease to Antibodies

II. Role of Conformation in Antigen Specificity

III. Toward Synthetic Vaccines: The MS-2 Bacteriophage Story

IV. Combined Use of Synthetic Antigens and Synthetic Adjuvants

V. Conclusion

References


14. Antigenic Determinants of Proteins and Synthetic Vaccines

I. Neutralization of Biologically Active Materials by Antibodies

II. The "Loop" Peptide: A Defined Antigenic Region of Lysozyme

III. Synthetic Peptides Inducing Antiviral Response

IV. Synthetic Vaccines?

References


15. Staphylococcal Nuclease as a Model Antigen

Text

References


16. Autoimmunity to Acetylcholine Receptor and Its Significance for Myasthenia Gravis

I. Acetylcholine Receptor, Myasthenia Gravis, and Experimental Autoimmune Myasthenia Gravis

II. Regulation of Experimental Autoimmune Myasthenia Gravis by Denatured Acetylcholine Receptor

III. Regulation of Experimental Autoimmune Myasthenia Gravis by Antiidiotypes

IV. Monoclonal Antibodies

V. Conclusion

References


17. The Antibody Combining Site: A Basis for a New Pharmacology

I. Review of the Potential Application of Antibodies to Human Pharmacology

II. Antibodies as Drugs

References

Part IV. Metabolism and Endocrinology


18. Lipoproteins and Atherosclerosis: A Problem in Cell Biology

I. The Anfinsen—Lipoprotein Lipase Connection

II. Approaches to Research on the Atherosclerosis-Lipoprotein Connection

III. Cells Involved in Low-Density Lipoprotein Degradation in Vivo

IV. Pathways Available for Catabolism of Native Low-Density Lipoprotein

V. Pathways for Catabolism of Modified Forms of Low-Density Lipid

VI. Role of Other Lipoproteins

References


19. Protein Chemistry and the Cardiologist

Text

References


20. Regulation of Cyclic Nucleotide Metabolism: From Proteins to Cyclic Nucleotides and Back

I. Cyclic Nucleotides and Some Enzymes That Metabolize Them

II. Adenylate Cyclase and Choleragen

III. ADP-Ribosylation of Proteins and the Future

References


21. Activation of Adenylate Cyclase in the Adrenal Cortex

I. The Nuclease Problem

II. The ACTH Problem

III. Concluding Remarks

References


22. Studies of Human Chorionic Gonadotropin: Implications for Fertility Research

I. Purification

II. Structure

III. Precursor Structure

IV. Biological Application

V. Immunochemical Distinction between hCG and hLH

References


23. Excursions of a Protein Vagabond: From Nuclease to Affinity Chromatography to Hormone Receptors and Membranes

Text

References

Part V· Genetics


24. Early Embryonic Development: Normal and Abnormal

Text

References


25. Molecular Regulation in Muscle Development

I. Lessons from Protein Folding and Virus Assembly

II. The Genetic Approach: From Phage Morphogenesis to Muscle Development

III. Structural Interactions of Myosin during the Assembly of Thick Filaments

IV. Coordinate Synthesis of Myosin Forms during Morphogenesis of Muscle

V. Gene Switching during Embryonic Muscle Differentiation

References


26. Interferon: Past, Present, and Future

I. Past and Present

II. Future

References


27. Parathyroid Hormone: Chemistry, Biosynthesis, and Mode of Action

I. Introduction

II. Physiology of Hormone Action

III. Isolation and Sequence Analysis

IV. Biosynthesis

V. Metabolism

VI. Mechanism of Action and Structure-Activity Relations of Parathyroid Hormone

VII. Summary

References

Bibliography

Index