Practical Protein Chemistry - A. Darbre 1989



From the Translators

Preface

References

Instead of an Introduction

Determination of the composition of protein oligomers. Preparation of monomers and polypeptide chains

Introduction

Methods for identification of oligomers

PAAG gradient electrophoresis

Determination of protein oligomer composition. Preparation of monomers and polypeptide chains

Methods for oligomer identification

Gel filtration

Determination of the composition of protein oligomers. Preparation of monomers and polypeptide chains

Identification of monomers

Methods for determining the molecular weight of monomers

Methods for isolation of monomers

Stoichiometric ratio of monomers in the oligomer

Determination of oligomer composition from molecular weights of monomers

Cross-linking of subunits with bifunctional reagents

Hybridization

Dissociation and Assembly

Polyacrylamide gel electrophoresis

Amino acid analysis

Determination of the composition of protein oligomers. Isolation of monomers and polypeptide chains

Cross-linking of oligomer and monomer

Disulfide bonds

Cross-linking of oligomers and monomers

Other types of cross-links in proteins

Determination of the composition of protein oligomers. Preparation of monomers and polypeptide chains

Preparation of monomers for sequencing

Hydrolysis of N-terminal pyroglutamic acid

Reduction of sulfoxides with N-methylmercaptoacetamide

Techniques for working with lipoproteins

Cleavage of oligosaccharide fragments from glycoproteins

Desalting

Determination of protein oligomer composition. Preparation of monomers and polypeptide chains

References

Chemical fragmentation of polypeptides

Introduction

Cleavage of disulfide bonds

Reduction and S-carboxymethylation

Chemical Fragmentation of Polypeptides

Cleavage of Disulfide Bonds

Other Protecting Groups (for the SH group)

Polypeptide Fragmentation by Chemical Methods

Cleavage of S-S Groups by Oxidation

Chemical fragmentation of polypeptides

Cleavage of disulfide bonds

Reaction with sulfite

Chemical Fragmentation of Polypeptides

Partial Acid Hydrolysis

Polypeptide Fragmentation by Chemical Methods

Cleavage of the Asp-Pro Bond

Chemical Fragmentation of Polypeptides

N-O Acyl Migration

Side Reactions

Polypeptide fragmentation by chemical methods

Cleavage at the methionine residue

Cyanogen bromide

Polypeptide Fragmentation by Chemical Methods

Cleavage at Methionine Residues

Other Reagents

Cleavage at Tryptophan Residues

Oxidative Halogenation

Chemical Fragmentation of Polypeptides

Cleavage Using BNPS-Skatole

Cleavage at Tryptophan Residues in the DMSO – Hydrohalic Acid System

Chemical fragmentation of polypeptides

Cleavage at tryptophan residues

Cleavage at tryptophan residues using cyanogen bromide in heptafluorobutyric acid

Chemical Fragmentation of Polypeptides

Cleavage at Tryptophan Residues

Cleavage at Tryptophan Residues with o-Iodosobenzoic Acid

Polypeptide Fragmentation by Chemical Methods

Other Reagents

Polypeptide fragmentation by chemical methods

Cleavage at the tryptophan residue

Ozonolysis

Polypeptide Fragmentation by Chemical Methods

Cleavage at Tyrosine Residues

N-Bromosuccinimide

Chemical fragmentation of polypeptides

Cleavage at tyrosine residues

Other reagents

Chemical Fragmentation of Polypeptides

Cleavage at Tyrosine Residues

Cleavage at Cysteine Residues

Polypeptide Fragmentation by Chemical Methods

Cyanylation with 2-Nitro-5-thiocyanobenzoic Acid

Chemical Fragmentation of Polypeptides

Other Methods of Chemical Peptide Bond Cleavage

Cleavage of the Asn-Gly Bond

Other Methods of Chemical Cleavage of Peptide Bonds

Cleavage at Proline Residues

Polypeptide Fragmentation by Chemical Methods

Cleavage at Histidine Residue

Other Methods of Chemical Peptide Bond Cleavage

Cleavage at the Dehydroalanine Residue

Other Methods of Chemical Cleavage of Peptide Bonds

Other Methods of Peptide Bond Cleavage

Chemical Fragmentation of Polypeptides

Conclusion

Chemical fragmentation of polypeptides

References

Enzymatic fragmentation of the polypeptide chain

Introduction

Preparation of the substrate

General conditions for enzymatic hydrolysis

Buffer solutions

Enzyme-to-substrate ratio

Temperature

Duration of enzymatic hydrolysis

Monitoring the enzymatic hydrolysis process

Termination of the enzymatic reaction

Protein modification methods

Cleavage of disulfide bonds

Alkylation of sulfhydryl groups

Fragmentation of the polypeptide chain by enzymatic methods

Modification of lysine residues

Enzymatic fragmentation of the polypeptide chain

Modification of arginine residues

Methods for protein modification

Modification of protein carboxyl groups

Fragmentation of the polypeptide chain by enzymatic methods

Proteases with high specificity

Enzymatic fragmentation of the polypeptide chain

High-specificity proteases

Trypsin

Fragmentation of the polypeptide chain by enzymatic methods

Proteases with high specificity

Thrombin

V8 Protease from Staphylococcus aureus

Fragmentation of the Polypeptide Chain by Enzymatic Methods

Proteases with High Specificity

Clostripain

Enzymatic fragmentation of the polypeptide chain

Proteases with high specificity

Submandibular gland protease

Protease from Armillaria mellea

Protease II from Myxobacter AL1

Fragmentation of the polypeptide chain by enzymatic methods

Postproline-specific enzyme

Enzymatic fragmentation of the polypeptide chain

Proteases with low specificity

Chymotrypsin

Fragmentation of Polypeptide Chains by Enzymatic Methods

Proteases with Low Specificity

Thermolysin

Enzymatic fragmentation of the polypeptide chain

Proteases with low specificity

Pepsin

Papain

Elastase

α-Lytic protease from Sorangium sp.

Conclusion

References

Disulfide Bonds

Introduction

Schematic Diagram of the Analysis

Determination of the Number of Disulfide Bonds

Disulphide bonds

Cleavage of the polypeptide chain into short cystine-containing peptides

Disulfide Bonds

Cleavage by cyanogen bromide

Pepsin Hydrolysis

Hydrolysis by trypsin and chymotrypsin

Hydrolysis by Staphylococcal Protease

Cleavage of the Polypeptide Chain into Short Cystine-Containing Peptides

Hydrolysis by Thermolysin

Cleavage of the polypeptide chain into short cystine-containing peptides

Hydrolysis following maleylation and succinylation

Fractionation of Cystine-Containing Peptides

Fractionation Methods

Detection of Cystine-Containing Peptides

Identification and Localization of Cystine-Containing Peptides

Cleavage of Disulfide Bonds

Disulfide bonds

Identification and localization of cystine-containing peptides

Identification based on a known amino acid sequence

Disulfide Bonds

Identification of disulfide bonds in proteins with unknown amino acid sequences

Disulfide bonds

General remarks

Disulfide Bonds

Special Methods

Dyes

Disulfide bonds

Special methods

Diagonal mapping

Disulfide Bonds

Special Methods

Specific Cleavage at Cysteine Residues

References

Affinity Chromatography of Proteins

Introduction

Applications of Affinity Chromatography

Methods for Preparation of Affinity Sorbent

Concept of Affinity Sorbent

Methods for Preparing Affinity Sorbents

Support Materials

Space Groups

Ligand

Condensation

Adsorption and Elution

General Procedures in Affinity Chromatography

Immobilized Lectins

General Techniques of Affinity Chromatography

Immobilized Antibodies

General Procedures in Affinity Chromatography

Immobilized Substrates, Inhibitors, and Enzyme Cofactors

Examples

Isolation and Purification of Antibodies

Purification of Hormone Receptors

Purification Strategy for Rare Proteins

References

Separation of Protein and Peptide Mixtures by High-Performance Liquid Chromatography

Introduction

Separation of protein and peptide mixtures by high-performance liquid chromatography

Gel filtration

Separation parameters

Gel chromatography

Chemical factors

Determination of true molecular weights

Adsorption and partition of polypeptides and proteins

Sample application preparation

Selection of columns for reversed-phase separation

Mobile phase

Reversed-phase separation of peptides

Selection of mobile phase composition

Isolation of peptides using phosphoric acid

Peptide separation using trifluoroacetic and heptafluorobutyric acids

Reversed-phase peptide separation

Correlation between retention and structure

High-speed liquid chromatography of proteins

Ion Exchange

References

Peptide Mapping of Proteins

Introduction

Peptide mapping of proteins

Peptide mapping — types of structures analyzed

Peptide mapping in practice

Cleveland mapping

Two-dimensional peptide mapping

Peptide Mapping of Proteins

Peptide Mapping in Practice

Peptide Mapping by High-Performance Liquid Chromatography

Peptide mapping of proteins

Conclusion

References

Analytical Methods

Introduction

Glass

Water

Hydrochloric acid

Concentration of Protein Solutions

Procedures

Exhaustive protein hydrolysis for amino acid analysis

Acid hydrolysis procedures

Tryptophan

Determination of tryptophan following alkaline protein hydrolysis

Determination of tryptophan following acid hydrolysis of protein

Determination of Tryptophan in Intact Proteins

Dicarboxylic amino acid amide residues

Methods for Amide Determination

Sulfur-containing amino acids

Methods of Determination

Arginine

Determination Methods

Phosphorylated Amino Acids

Protein Hydrolysis

Methods of Analysis

y-Carboxyglutamic Acid

Protein Hydrolysis

y-Carboxyglutamic acid

Methods of Analysis

Analytical methods

Acetyl and formyl groups

Analytical Methods

Determination of acetyl and formyl groups

Detection of compounds in paper chromatography and thin-layer chromatography

Fluorescent detection methods

Detection of compounds in paper and thin-layer chromatography

Detection using ninhydrin

Mixed detection methods

Thin-Layer Chromatography of Amino Acids

Separation Methods

Amino Acid Column Chromatography

Columns and Buffers

Internal Standards

Determination of Amino Acids

Gas-Liquid Chromatography of Amino Acids

General Sample Preparation Procedure

Quantitative Protein Determination

Protein Determination Using the Folin–Ciocalteu Reagent

Protein Determination Using the Biuret Reaction

Protein Determination Using Coomassie Brilliant Blue

Protein Determination Using Sulfobromophthalein

Protein Determination Using Trinitrobenzenesulfonic Acid in the Presence of Lipids

Atomic Absorption Spectrophotometry Method

Spectrophotometric Methods

Methods for Staining Proteins in Gels

Protein Staining Methods Using Dyes

Protein Staining Methods in Gels

Protein Staining with Silver Complexes

Protein Staining on Nitrocellulose Paper

Amido Black Staining

Staining with Indian Ink

Detection Using Antibodies

Detection Using Silver and Antibody Complexes

Determination of Protein Bound to a Solid Support

Matrix-Bound Protein

Sepharose-Bound Protein

Determination of protein bound to a solid support

Determination of amino groups on a solid support

Determination of protein attached to a solid support

Determination of amino groups on hydrophilic matrices

Determination of amino groups by reaction with chloranil

Determination of Protein Bound to a Solid Support

Determination of the Nature of the Resin Substituent by Staining

Determination of protein attached to a solid support

Colorimetric determination of carbodiimides

Fluorometric determination of carbodiimide

Glycoproteins

Introduction

Carbohydrate-Containing Proteins

Methyl Glycoside Trimethylsilyl Method

Sensitive Methyl Glycoside Trimethylsilyl Method

Gas Chromatography-Mass Spectrometry Method

Determination of neutral sugars and aminosugars as alditol acetates by GLC

Glycoproteins

Determination of alditols by thin-layer and gas-liquid chromatography

Carbohydrate-Containing Proteins

Determination of neutral sugars and aminosugars on an amino acid analyzer

Acknowledgements

Enantiomeric analysis of amino acid mixtures by high-performance liquid chromatography

Introduction

Reagents

Synthesis of N, N-di-n-propyl-L-alanine

HPLC Solutions

HPLC

Group separation

Enantiomeric analysis

Conclusions

Acknowledgements

References

Traditional strategy for protein structure determination

Introduction

Choosing a research strategy

Enzymatic hydrolysis

Fractionation of soluble peptides

Traditional strategy for determining protein structure

Gel filtration

Traditional Strategy for Protein Structure Determination

Fractionation of Soluble Peptides

Dowex-50 Column Chromatography

Traditional strategy for determining protein structure

Fractionation of soluble peptides

DEAE-cellulose column chromatography

High-voltage electrophoresis and paper chromatography

Traditional strategy for protein structure determination

Fractionation of insoluble peptides

Homogeneity control and determination of the amino acid sequence of peptides

Reconstruction of the polypeptide chain

Methods

Preparative electrophoresis and paper chromatography

Traditional strategy for determining protein structure

Staining of peptides

Traditional strategy for protein structure determination

Peptide elution

References

Determination of the amino acid sequence of peptides by the Edman degradation method with identification of dansyl amino acids

Introduction

Dansylation

Dansylation procedure

Determination of the amino acid sequence of peptides by the Edman method with identification of dansyl amino acids

Edman condensation and cleavage

Edman degradation. Methodology

References

Methods for Solid-Phase Amino Acid Sequence Analysis

Introduction

Materials

Solvents

Methods of solid-phase amino acid sequence analysis

Reagents

Methods for Solid-Phase Amino Acid Sequence Analysis

Glass beads for diluting polymer samples

Supports

Coupling Buffers

Reagent and Buffer Solutions for the Sequenator

Methods of Solid-Phase Amino Acid Sequence Analysis

Resin Synthesis

Polystyrene-Based Resins

Methods for Solid-Phase Amino Acid Sequence Analysis

Glass-Based Supports

Methods of Solid-Phase Amino Acid Sequence Analysis

Determination of Amino Group Content in Supports Based on Organic Polymers or Porous Glasses

Methods for Solid-Phase Amino Acid Sequence Analysis

Coupling Methods

Coupling of Lysyl-Containing Peptides Using DITC

Methods of solid-phase amino acid sequence analysis

Attachment methods

DITC method using isothiocyanate glass

Methods of solid-phase amino acid sequencing

Coupling methods

Coupling via homoserine lactone

Methods of solid-phase amino acid sequence analysis

Carboxyl coupling using carbodiimide

Monitoring coupling efficiency

Methods of solid-phase amino acid sequencing

Cleavage on a solid-phase sequencer

Column

Methods of solid-phase amino acid sequence analysis

Column packing

Methods for Solid-Phase Amino Acid Sequence Analysis

Cleavage on a Solid-Phase Sequenator

Sequenator Operational Program

Carbamoylation Reaction

Cleavage in a Solid-Phase Sequenator

Solvents

Cleavage on a Solid-Phase Sequenator

Cleavage of Anilinothiazolinone

Rearrangement of Anilinothiazolinone into PTH

Discussion

Solid-Phase Analysis of Small Peptides

Solid-Phase Analysis of Large Peptides and Proteins

Comparison of Liquid-Phase and Solid-Phase Methods

Microscale Structure Analysis

References

Analysis of Amino Acid Phenylthiohydantoins

Introduction

Analytical Methods

High-Performance Liquid Chromatography

Analysis of amino acid phenylthiohydantoins

Gas-Liquid Chromatography

Analysis of Amino Acid Phenylthiohydantoins

Thin-Layer Chromatography

Analysis of amino acid phenylthiohydantoins

Back-hydrolysis of PTH-amino acid derivatives

Analysis of Amino Acid Phenylthiohydantoins

References

Determination of amino acid sequence using 4-dimethylaminoazobenzene-4'-isothiocyanate (manual procedure)

Introduction

Determination of Amino Acid Sequence Using 4-Dimethylaminoazobenzene-4'-isothiocyanate (Manual Procedure)

Reagents and Solvents

Determination of amino acid sequence using 4-dimethylaminoazobenzene-4'-isocyanate (manual procedure)

DABITC-FITC liquid-phase method

DABITC–FITC solid-phase methodology

Determination of amino acid sequence using 4-dimethylaminoazobenzene-4'-isothiocyanate (manual procedure)

Conversion of amino acid thiazolinones to thiohydantoins

Identification of DABTC-amino acids

Thin-layer chromatography

Amino acid sequence determination using 4-dimethylaminoazobenzene-4'-isothiocyanate (manual procedure)

Identification of DABTC amino acids

High-Performance Liquid Chromatography

Determination of Amino Acid Sequence Using 4-Dimethylaminoazobenzene-4'-isothiocyanate (Manual Procedure)

Conclusion

References

Current state of automated liquid-phase amino acid sequence analysis

Introduction

Sample preparation

Comparison of Quadrol with volatile buffers

Polybrene

Reagents and solvents

Key challenges encountered when using an automated sequencer

Vacuum system

Major problems encountered when using an automated sequencer

Vacuum line leaks in a single-pump system

Major challenges encountered when using an automated sequencer

Programming unit

Main problems arising from the use of an automated sequencer

Relay

Major problems encountered when using an automated sequencer

Valves

Instrument performance quality control

References

The latest methods for solid-phase and liquid-phase amino acid sequence determination

Introduction

Latest methods of solid-phase and liquid-phase amino acid sequence determination

Solid-Phase Analysis. Novel Approaches

General Remarks

The latest methods of solid-phase and liquid-phase amino acid sequence determination

Solid-Phase Analysis. The Latest Approaches

Supports

Latest methods for solid-phase and liquid-phase amino acid sequence determination

Solid-Phase Analysis: The Latest Approaches

Attachment of peptides to supports and "blocking" of the remaining reactive sites of the support

The latest methods for solid-phase and liquid-phase determination of amino acid sequences

Edman Degradation

Latest methods for solid-phase and liquid-phase amino acid sequence determination

Solid-Phase Analysis. Recent Approaches

Other Sequential Degradation Methods

The latest methods for solid-phase and liquid-phase amino acid sequence determination

Automatic liquid-phase analysis. Improved procedures

Analysis of proteins and large peptides at the conventional level

Latest methods for solid-phase and liquid-phase amino acid sequence determination

Automated liquid-phase analysis. Advanced procedures

Amino acid sequence analysis of small and hydrophobic peptides

Latest methods of solid-phase and liquid-phase amino acid sequence determination

Automatic liquid-phase analysis. Advanced techniques

Microscale analysis

Latest methods for solid-phase and liquid-phase amino acid sequence determination

Conclusion

State-of-the-art methods for solid-phase and liquid-phase amino acid sequencing

References

Amino acid sequence analysis at the micro level using a gas-phase peptide-protein sequencer

Introduction

Micro-scale amino acid sequence analysis using a gas-phase peptide-protein sequencer

Sequencer

Reactor

Reagents and solvents

Microscale amino acid sequence analysis using a gas-phase peptide-protein sequencer

Sequencer Operation

Micro-scale amino acid sequence analysis using a gas-phase peptide-protein sequencer

Polypeptide purification for microanalysis

Reagents and Materials

Instrumentation and Methodology

Discussion

Sample immobilization and instrument sensitivity

Microscale amino acid sequence analysis using a gas-phase peptide-protein sequencer

Chemical aspects

Micro-scale amino acid sequence analysis using a gas-phase peptide-protein sequencer

Amount of sample analyzed

Prospects

References

Determination of C-terminal amino acid sequence

Introduction

Isolation and identification of C-terminal peptides

Methods of ion-exchange chromatography

Solid-phase resins

Determination of C-Terminal Amino Acid Sequence

Isolation and Identification of C-Terminal Peptides

Two-Dimensional Peptide Mapping

Determination of C-Terminal Groups

Selective Tritium Labelling

Determination of the C-terminal amino acid sequence

Determination of C-terminal groups

Hydrazinolysis

Determination of C-terminal amino acid sequence

Selective reduction

Determination of C-terminal amino acids as aldehydes

Determination of C-terminal amino acids via oxazolone alcoholysis

Determination of the C-terminal amino acid sequence

Determination of the C-terminal sequence

Cleavage by means of thiocyanate

Determination of C-terminal amino acid sequence

Determination of C-terminal sequence

Cleavage using cyanamide

Other chemical cleavage methods

Determination of the C-terminal amino acid sequence

Determination of the C-terminal sequence

Carboxypeptidases

Determination of C-Terminal Amino Acid Sequence

Conclusion

Determination of the C-terminal amino acid sequence

References

Application of electron impact mass spectrometry for determining the amino acid sequence of peptides and proteins

Introduction

Requirements for the analyzed peptides

Molecular dimensions

Sample size

Sample purity

Requirements for analytical instruments

Sample preparation methods

Reagent purification

Laboratory glassware

Hydrazinolysis

Acetylation

Permethylation

Recording mass spectra

General principles of mass spectrometric determination of the amino acid sequence of peptides and proteins

Interpretation of Mass Spectra

Introduction

Interpretation of mass spectra

Peptide fragmentation pathways

Interpretation of Mass Spectra

Introduction of a 2H-Label

Special cases of application of the method

Peptides with a blocked N-terminal amino group

Application of Electron Impact Mass Spectrometry for Determining the Amino Acid Sequence of Peptides and Proteins

Special Cases of Method Application

Determination of the N-Terminal Amino Acid Sequence

Application of electron impact mass spectrometry for determining the amino acid sequence of peptides and proteins

Special cases of method application

Proteins containing γ-carboxyglutamic acid residues

Application of Electron Impact Mass Spectrometry for Determining the Amino Acid Sequence of Peptides and Proteins

Conclusion

Application of Electron Impact Mass Spectrometry to Determine the Amino Acid Sequence of Peptides and Proteins

References

X-Ray Crystallography and Electron Microscopy

X-Ray Diffraction

Introduction

X-ray crystallography and electron microscopy

Molecular imaging as a method of structural analysis

X-ray diffraction

Imaging of molecules: a type of structural analysis

Principles of structure determination in X-ray structural analysis

X-ray Crystallography and Electron Microscopy

X-ray Diffraction

Protein Crystallography

X-Ray Crystallography and Electron Microscopy

X-Ray Diffraction

Model Building

X-ray Crystallography and Electron Microscopy

X-ray Diffraction

Computer-Aided Molecular Modeling

Electron Microscopy

Introduction

X-ray crystallography and electron microscopy

Electron microscopy

Resolution and limitations of the method

Electron microscope

X-ray Crystallography and Electron Microscopy

Electron Microscopy

Technical Challenges

Sample Preparation and Staining

X-ray crystallography and electron microscopy

Electron microscopy

Image processing

X-ray Crystallography and Electron Microscopy

Electron Microscopy

Three-Dimensional Electron Microscopy

Molecular Microscopy

X-ray crystallography and electron microscopy

References

Prediction of Peptide and Protein Conformation

Introduction

Traditional Methods

Limitations of Traditional Methods

An Arsenal of Modern Theoretical Methods

The Arsenal of Modern Theoretical Methods

Quantum Mechanical Methods

An Arsenal of Modern Theoretical Methods

The Molecular Dynamics Method

The Arsenal of Modern Theoretical Methods

Monte Carlo Method

Statistical Mechanics

Minimization

Rigid Geometry

Periodic Evaluation and Mapping

An Arsenal of Modern Theoretical Methods

Heuristic Methods

Secondary Structure Prediction. Special Calculation Methods

Basic Assumptions for Calculations

Basic premises of calculations

Testing of potential functions derived from crystallographic data using simple approximate methods

Initial Prerequisites for Calculations

Testing of Potential Functions Derived from Structural Data Using More Precise Methods

Basic Assumptions of Calculations

Attempts to Predict the Tertiary Structure of Globular Proteins

Current State of Prediction Methods

References