INTRODUCTION REACTIVE GROUPS OF PROTEINS AND THEIR MODIFYING AGENTS Compositions of Proteins Functional Groups of Proteins Group Directed Reagents CHOICE AND DESIGN OF CROSS-LINKING REAGENTS Nucleophilic Reactions Electrophilic Reactions Group Directed Reactions Nonspecific Reactions Cleavable Reagents Labeled Cross-Linking Reagents Hydrophobicity and Hydrophilicity of Reagents HOMOBIFUNCTIONAL CROSS-LINKING REAGENTS Amino Group Directed Cross-Linkers Sulfhydryl Group Directed Cross-Linkers Carboxyl Group Directed Cross-Linking Reagents Phenolate and Imidazolyl Group Directed Cross-Linking Reagents Arginine Residue Directed Cross-Linker Nondiscriminatory Photoactivatable Cross-Linkers Noncovalent Homobifunctional Cross-Linking Reagents Miscellaneous Bifunctional Reagents HETEROBIFUNCTIONAL CROSS-LINKERS Group Selective Heterobifunctional Cross-Linking Reagents Photosensitive Heterobifunctional Cross-Linking Reagents Disguised or Masked Reagents ZERO-LENGTH CROSS-LINKING REAGENTS Carboxyl Group Activating Reagents Reagents for Carbohydrate Activation Reagents for Disulfide Formation Enzymes as Zero-Length Cross-Linkers PROCEDURES, ANALYSIS, AND COMPLICATIONS Procedures for Cross-Linking Analysis of Cross-Linked Products Reaction Complications APPLICATION OF CHEMICAL CROSS-LINKING TO SOLUBLE PROTEINS Interresidue Distance Determinations Nearest Neighbor Analysis Conformational Analysis Structural Stability CROSS-LINKING OF MEMBRANE PROTEINS General Methodology of Membrane Cross-Linking Possible Artifacts of Membrane Cross-Linking Identification of Membrane Receptors Nearest-Neighbor Analysis of Membrane Components Membrane Protein Conformational Analysis Stabilization of Membrane Proteins PREPARATION OF ENZYME IMMUNOCONJUGATES AND OTHER IMMUNOASSAY COMPONENTS Components of Enzyme Immunoassays Conjugation of Enzymes to Antibodies and their Fragments Coupling Proteins to Antibodies and their Fragments Coupling Enzymes to Proteins and Antigens Characterization of Conjugation Methods PREPARATION OF IMMUNOTOXINS AND OTHER DRUG CONJUGATES FOR TARGETING THERAPEUTICS Selection of Cross-Linking Reagents and Toxins Conjugation through Disulfide Bond Conjugation through Thioether Linkage Conjugation with Actuvated Chlorambucil Conjugation with Acid-Labile and Photocleaveable Cross-Linkers Conjugation through Carbohydrate Residues Preparation of Immunotoxins Using Avidin-Biotin Linkage Miscellaneous Coupling Methods CONJUGATION OF PROTEINS TO SOLID MATRICES Functionalities of Matrices Protein Immobilization by Matrix Activation Cross-Linking Reagents Used in Protein Immobilization Cross-Linking through Carbohydrate Chains OTHER APPLICATIONS AND FUTURE PROSPECTS Application to Nucleic Acids Cross-Linking Small Molecules to Proteins Synopsis INDEX Note: Each chapter also contains an Introduction and References.