BIOLOGICAL CHEMISTRY: INTRODUCTION TO THE CHEMISTRY OF LIFE AMINO ACIDS AND PROTEINS
CONTENTS MASS SPECTROMETRY OF AMINO ACIDS AND PROTEINS INTRODUCTION MASS TERMINOLOGY COMPONENTS OF A MASS SPECTROMETER RESOLUTION AND MASS ACCURACY ACCURATE ANALYSIS OF ESI MULTIPLY CHARGED IONS FRAGMENT IONS BASIC PROTEIN CHEMISTRY AND HOW IT RELATES TO MS MASS PROPERTIES OF THE POLYPEPTIDE CHAIN IN VIVO PROTEIN MODI?CATIONS EX VIVO PROTEIN MODI?CATIONS SAMPLE PREPARATION AND DATA ACQUISITION TOP-DOWN VERSUS BOTTOM-UP PROTEOMICS SHOTGUN VERSUS TARGETED PROTEOMICS ENZYMATIC DIGESTION FOR BOTTOM-UP PROTEOMICS LIQUID CHROMATOGRAPHY AND CAPILLARY ELECTROPHORESIS FOR MIXTURES IN BOTTOM-UP DATA ANALYSIS OF LC-MS/MS (OR CE-MS/MS) OF MIXTURES IDENTI?CATION OF PROTEINS FROM MS/MS SPECTRA OF PEPTIDES DE NOVO SEQUENCING MS OF PROTEIN STRUCTURE, FOLDING, AND INTERACTIONS METHODS TO MASS-TAG STRUCTURAL FEATURES CONCLUSIONS AND PERSPECTIVES REFERENCES X-RAY STRUCTURE DETERMINATION OF PROTEINS AND PEPTIDES LIGHT MICROSCOPY X-RAYS AND CRYSTALLOGRAPHY AT THE START X-RAY CRYSTALLOGRAPHY TODAY LIMITATIONS OF X-RAY CRYSTALLOGRAPHY GROWING CRYSTALS WHY CRYSTALS? BASIC METHODS OF GROWING PROTEIN CRYSTALS PROTEIN SAMPLE PRELIMINARY CRYSTAL ANALYSIS MOUNTING CRYSTALS FOR X-RAY ANALYSIS SYMMETRY AND SPACE GROUPS CRYSTALS AND THE UNIT CELL POINT GROUPS SPACE GROUPS ASYMMETRIC UNIT X-RAY SCATTERING AND DIFFRACTION X-RAYS AND MATHEMATICAL REPRESENTATION OF WAVES INTERACTION OF X-RAYS WITH MATTER CRYSTAL LATTICE, MILLER INDICES, AND THE RECIPROCAL SPACE X-RAY DIFFRACTION FROM A CRYSTAL: BRAGG’S LAW BRAGG’S LAW IN RECIPROCAL SPACE FOURIER TRANSFORM EQUATION FROM A LATTICE FRIEDEL’S LAW AND THE ELECTRON DENSITY EQUATION COLLECTING AND PROCESSING DIFFRACTION DATA DATA COLLECTION STRATEGY SYMMETRY AND SCALING DATA SOLVING THE STRUCTURE (DETERMINING PHASES) MOLECULAR REPLACEMENT ISOMORPHOUS REPLACEMENT MAD ANALYZING AND RE?NING THE STRUCTURE ELECTRON DENSITY INTERPRETATION AND MODEL BUILDING PROTEIN STRUCTURE RE?NEMENT PROTEIN STRUCTURE VALIDATION NUCLEAR MAGNETIC RESONANCE OF AMINO ACIDS, PEPTIDES, AND PROTEINS ACTIVE NUCLEI IN NMR ENERGY LEVELS AND SPIN STATES MAIN NMR PARAMETERS (GLOSSARY) CHEMICAL SHIFT SCALAR COUPLING CONSTANTS NOE RDC AMINO ACIDS HISTORICAL SIGNI?CANCE AMINO ACIDS STRUCTURE RANDOM COIL CHEMICAL SHIFT SPIN SYSTEMS LABILE PROTONS CONTEMPORARY RELEVANCE: METABOLOMICS PEPTIDES OLIGOPEPTIDES AS MODELS FOR CONFORMATIONAL TRANSITIONS IN PROTEINS BIOACTIVE PEPTIDES CHOICE OF THE SOLVENT TRANSPORT FLUIDS MEMBRANES RECEPTOR CAVITIES ENSEMBLE CALCULATIONS SELECTED EXAMPLES FROM THE MAJOR FIELDS OF BIOACTIVE PEPTIDES ASPARTAME OPIOIDS TRANSMEMBRANE HELICES CYCLOPEPTIDES PROTEINS AN ALTERNATIVE TO OR A VALIDATION OF DIFFRACTOMETRIC METHODS? PROTEIN SPECTRA WÜTHRICH’S PROTOCOL SAMPLE PREPARATION RECORDING NMR SPECTRA SEQUENTIAL ASSIGNMENT CONFORMATIONAL CONSTRAINTS MODEL BUILDING RECENT DEVELOPMENTS SELECTED STRUCTURES SUPEROXIDE DISMUTASES MALATE SYNTHASE G INTERACTIONS CONCLUSIONS STRUCTURE AND ACTIVITY OF N-METHYLATED PEPTIDES CONFORMATIONAL EFFECTS OF N-METHYLATION EFFECTS OF N-METHYLATION ON BIOACTIVE PEPTIDES THYROTROPIN-RELEASING HORMONE CYCLIC PEPTIDES SOMATOSTATIN ANALOGS ANTIMALARIAL PEPTIDE CONCLUDING REMARKS HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY OF PEPTIDES AND PROTEINS BASIC TERMS AND CONCEPTS IN CHROMATOGRAPHY CHEMICAL STRUCTURE OF PEPTIDES AND PROTEINS BIOPHYSICAL PROPERTIES OF PEPTIDES AND PROTEINS CONFORMATIONAL PROPERTIES OF PEPTIDES AND PROTEINS OPTICAL PROPERTIES OF PEPTIDES AND PROTEINS HPLC SEPARATION MODES IN PEPTIDE AND PROTEIN ANALYSIS SEC RPC NPC HILIC ANPC HIC IEX METHOD DEVELOPMENT FROM ANALYTICAL TO PREPARATIVE SCALE ILLUSTRATED FOR HP-RPC DEVELOPMENT OF AN ANALYTICAL METHOD SCALING UP TO PREPARATIVE CHROMATOGRAPHY FRACTIONATION ANALYSIS OF THE QUALITY OF THE FRACTIONATION MULTIDIMENSIONAL HPLC PURI?CATION OF PEPTIDES AND PROTEINS BY MD-HPLC METHODS FRACTIONATION OF COMPLEX PEPTIDE AND PROTEIN MIXTURES BY MD-HPLC OPERATIONAL STRATEGIES FOR MD-HPLC METHODS OFF-LINE COUPLING MODE FOR MD-HPLC METHODS ON-LINE COUPLING MODE FOR MD-HPLC METHODS DESIGN OF AN EFFECTIVE MD-HPLC SCHEME ORTHOGONALITY OF CHROMATOGRAPHIC MODES COMPATIBILITY MATRIX OF CHROMATOGRAPHIC MODES LOCAL SURFACE PLASMON RESONANCE AND ELECTROCHEMICAL BIOSENSING SYSTEMS FOR ANALYZING FUNCTIONAL PEPTIDES LOCALIZED SURFACE PLASMON RESONANCE (LSPR)-BASED MICRO?UIDICS BIOSENSOR FOR THE DETECTION OF INSULIN PEPTIDE HORMONE LSPR AND MICRO TOTAL ANALYSIS SYSTEMS MICRO?UIDIC LSPR CHIP FABRICATION AND LSPR MEASUREMENT DETECTION OF THE INSULIN–ANTI-INSULIN ANTIBODY REACTION ON A CHIP ELECTROCHEMICAL LSPR-BASED LABEL-FREE DETECTION OF MELITTIN MELITTIN AND E-LSPR FABRICATION OF E-LSPR SUBSTRATE AND FORMATION OF THE HYBRID BILAYER MEMBRANE MEASUREMENTS OF MEMBRANE-BASED SENSORS FOR PEPTIDE TOXIN LABEL-FREE ELECTROCHEMICAL MONITORING OF B-AMYLOID (AB) PEPTIDE AGGREGATION ALZHEIMER’S AB AGGREGATION AND ELECTROCHEMICAL DETECTION METHOD LABEL-FREE ELECTROCHEMICAL DETECTION OF AB AGGREGATION SURFACE PLASMON RESONANCE SPECTROSCOPY IN THE BIOSCIENCES SPR-BASED OPTICAL BIOSENSORS PRINCIPLE OF OPERATION OF SPR BIOSENSORS DESCRIPTION OF A SPR INSTRUMENT SENSOR SURFACE FLOW SYSTEM DETECTION SYSTEM APPLICATION OF SPR IN IMMUNOSENSOR DESIGN ASSAY DEVELOPMENT IMMOBILIZATION OF THE ANALYTE TO A SPECI?C CHIP SURFACE ASSAY DESIGN APPLICATION OF SPR IN MEMBRANE INTERACTIONS GENERAL PROTOCOLS FOR MEMBRANE INTERACTION STUDIES BY SPR LIPOSOME PREPARATION FORMATION OF BILAYER SYSTEMS ANALYTE BINDING TO THE MEMBRANE SYSTEM MEMBRANE BINDING OF ANTIMICROBIAL PEPTIDES BY SPR DATA ANALYSIS LINEARIZATION ANALYSIS NUMERICAL INTEGRATION ANALYSIS STEADY-STATE APPROXIMATIONS ATOMIC FORCE MICROSCOPY OF PROTEINS FOREWORD IMPORTANCE OF ASKING THE RIGHT QUESTION AFM PRINCIPLE AND BASIC MODES OF OPERATION HOW DOES A TIP TAP? BIOIMAGING HIGHLIGHTS PROTEIN OLIGOMERIZATION, AGGREGATION, AND FIBERS MEMBRANE BINDING AND LYSIS ION CHANNEL ACTIVITY PROTEIN–DNA-SPECI?C BINDING ISSUES RESOLUTION IMAGING FORCE REPETITIVE STRESS ARTIFACTS RELATED TO TOO LOW FREE AMPLITUDE TRANSIENT FORCE AND BANDWIDTH ACCURACY OF SURFACE TRACKING STEP ARTIFACTS FORCE MEASUREMENTS LIQUID IMAGING SAMPLE PREPARATION FOR BIOIMAGING ADHESION PHYSICAL ENTRAPMENT CHEMICAL BINDING OUTLOOK SOLVENT INTERACTIONS WITH PROTEINS AND OTHER MACROMOLECULES SOLVENT APPLICATIONS RESEARCH PRECIPITATION CHROMATOGRAPHY PROTEIN REFOLDING FORMULATION SOLVENT APPLICATION FOR VIRUSES ISOLATION AND PURI?CATION OF VIRUSES STABILIZATION AND FORMULATION OF VIRUSES INACTIVATION OF VIRUSES SOLVENT APPLICATION FOR DNA ISOLATION AND PURI?CATION OF DNA STABILITY OF DNA IN A COSOLVENT SYSTEM MECHANISM PHYSICAL MECHANISM HYDRATION EXCLUDED VOLUME THERMODYNAMIC INTERACTION GROUP INTERACTION: MODEL COMPOUND SOLUBILITY PREFERENTIAL INTERACTION PROTEIN–SOLVENT INTERACTIONS IN FROZEN AND FREEZE-DRIED SYSTEMS FROZEN SYSTEMS FREEZE-DRIED SYSTEM ROLE OF CYSTEINE SULFUR: A REDOX CHAMELEON WITH MANY FACES THREE FACES OF THIOLS: NUCLEOPHILICITY, REDOX ACTIVITY, AND METAL BINDING TOWARDS A DYNAMIC PICTURE OF DISUL?DE BONDS CHEMICAL PROTECTION AND REGULATION VIA S-THIOLATION ‘‘DORMANT’’ CATALYTIC SITES PEROXIREDOXIN/SUL?REDOXIN CATALYSIS AND CONTROL PATHWAY HIGHER SULFUR OXIDATION STATES: FROM THE SHADOWS TO THE HEART OF BIOLOGICAL SULFUR CHEMISTRY CYSTEINE AS A TARGET FOR OXIDANTS, METAL IONS, AND DRUG MOLECULES CONCLUSIONS AND OUTLOOK ROLE OF DISULFIDE BONDS IN PEPTIDE AND PROTEIN CONFORMATION PROBING THE ROLE OF DISUL?DE BONDS CONTRIBUTION OF DISUL?DE BONDS TO PROTEIN STABILITY ROLE OF DISUL?DE BONDS IN PROTEIN FOLDING ROLE OF INDIVIDUAL DISUL?DE BONDS IN PROTEIN STRUCTURE DISUL?DE BONDS IN PROTEIN DYNAMICS DISUL?DE BONDING PATTERNS AND PROTEIN TOPOLOGY CONSERVATION AND EVOLUTION OF DISUL?DE BONDING PATTERNS CONSERVATION OF DISUL?DE BONDS CYSTEINE FRAMEWORK AND DISUL?DE CONNECTIVITY NON-NATIVE DISUL?DE CONNECTIVITIES APPLICATIONS QUANTITATIVE MASS SPECTROMETRY-BASED PROTEOMICS QUANTI?CATION IN BIOLOGICAL MS LABEL-FREE APPROACHES IN QUANTITATIVE MS PROTEOMICS SIL IN QUANTITATIVE PROTEOMICS IDENTIFYING PROTEINS INTERACTING WITH SMALL MOLECULES WITH QUANTITATIVE PROTEOMICS TWO-DIMENSIONAL GEL ELECTROPHORESIS AND PROTEIN/POLYPEPTIDE ASSIGNMENT AIM OF PROTEIN ANALYSIS AND DEVELOPMENT OF 2-DE TECHNIQUES CURRENT STATUS OF 2-DE TECHNIQUES DENATURING 2-DE FOR THE SEPARATION OF POLYPEPTIDES PRINCIPLE PROCEDURES SPECI?C FEATURES NONDENATURING 2-DE FOR THE SEPARATION OF BIOLOGICALLY ACTIVE PROTEINS AND PROTEIN COMPLEXES BLUE-NATIVE 2-DE FOR THE DETECTION OF PROTEIN–PROTEIN INTERACTIONS VISUALIZATION OF PROTEINS SEPARATED ON 2-DE GELS FIXING BEFORE CBB, SILVER, OR FLUORESCENT DYE STAINING CBB STAINING SILVER STAINING REVERSE STAINING WITH ZINC-IMIDAZOLE FLUORESCENT DYE STAINING QUANTITATION DEVELOPMENT OF PROTEIN ASSIGNMENT TECHNIQUES ON 2-DE GELS AND CURRENT STATUS OF MASS SPECTROMETRIC TECHNIQUES DEVELOPMENT OF PROTEIN ASSIGNMENT TECHNIQUES MS-BASED ASSIGNMENT TECHNIQUES UTILIZING AMINO ACID SEQUENCE DATABASES SAMPLE PREPARATION FOR MS ANALYSIS MALDI-TOF-MS AND PMF MS/MS AND PEPTIDE SEQUENCE SEARCH BIOINFORMATICS TOOLS FOR DETECTING POST-TRANSLATIONAL MODIFICATIONS IN MASS SPECTROMETRY DATA PTM DISCOVERY WITH MS DETECTING PTMS IN MS AND MS/MS DATA DISCOVERING PTMS IN MS OR MS/MS DATA PTM PREDICTION TOOLS FROM MS DATA FROM SEQUENCE DATA DATABASE RESOURCES FOR PTM ANALYSIS