Thermodynamics and kinetics of drug binding:
Gespeichert in:
| Weitere Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Weinheim
Wiley-VCH
2015
|
| Schriftenreihe: | Methods and principles in medicinal chemistry
65 |
| Schlagworte: | |
| Online-Zugang: | Inhaltstext Inhaltsverzeichnis |
| Beschreibung: | XXIII, 334 S. Ill., graph. Darst. 240 mm x 170 mm |
| ISBN: | 9783527335824 9783527673049 9783527673056 9783527673032 9783527673025 |
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CONTENTS
LIST OF CONTRIBUTORS XIII
PREFACE XIX
A PERSONAL FOREWORD XXI
SECTION I: THERMODYNAMICS 1
1 THE
BINDING THERMODYNAMICS OF DRUG CANDIDATES 3
ERNESTO FREIRE
1.1 AFFINITY OPTIMIZATION 3
1.2 THE BINDING AFFINITY 4
1.3 THE ENTHALPY CHANGE
6
1.4 THE ENTROPY CHANGE 7
1.5 ENGINEERING BINDING CONTRIBUTIONS 9
1.6 LIPOPHILIC EFFICIENCY AND BINDING ENTHALPY 11
ACKNOWLEDGMENTS 12
REFERENCES 12
2 VAN'T HOFF BASED THERMODYNAMICS IS
KATIA
VARANI,
STEFANIA
GESSI,
STEFANIA MERIGHI, AND PIER ANDREA BOREA
2.1 RELEVANCE OF THERMODYNAMICS TO PHARMACOLOGY 15
2.2 AFFINITY CONSTANT DETERMINATION 16
2.3 THE ORIGIN OF VAN'T HOFF EQUATION 17
2.4 FROM VAN'T HOFF TOWARD THERMODYNAMIC DISCRIMINATION 18
2.5 REPRESENTATION OF AG, AH", AND A5 DATA 20
2.6 THE ADENOSINE RECEPTORS BINDING THERMODYNAMICS STORY 21
2.7 BINDING THERMODYNAMICS OF G-PROTEIN COUPLED RECEPTORS 25
2.8 BINDING THERMODYNAMICS OF LIGAND-GATED ION CHANNEL
RECEPTORS 26
2.9 DISCUSSION 29
ABBREVIATIONS 31
REFERENCES 32
HTTP://D-NB.INFO/1059940248
VII CONTENTS
3 COMPUTATION OF DRUG-BINDING THERMODYNAMICS 37
GYORGY G. FERENCZY
3.1 INTRODUCTION 37
3.2 POTENTIAL OF MEAN FORCE CALCULATIONS 39
3.3 ALCHEMICAL TRANSFORMATIONS 41
3.4 NONEQUILIBRIUM METHODS 44
3.5 MM-PBSA 44
3.6 LINEAR INTERACTION ENERGY 47
3.7 SCORING FUNCTIONS 48
3.8 FREE-ENERGY COMPONENTS 50
3.8.1 CALCULATION OF ENTHALPY 50
3.8.2 CALCULATION OF ENTROPY 51
3.9 SUMMARY 52
REFERENCES 52
4 THERMODYNAMICS-GUIDED OPTIMIZATIONS IN MEDICINAL CHEMISTRY 63
GYORGY M. KESERII
4.1 INTRODUCTION 63
4.2 THE THERMODYNAMICS OF MEDICINAL CHEMISTRY OPTIMIZATIONS
66
4.3 SELECTION OF SUITABLE STARTING POINTS 70
4.4 THERMODYNAMICS BASED OPTIMIZATION STRATEGIES 73
REFERENCES 78
5 FROM MOLECULAR UNDERSTANDING TO STRUCTURE-THERMODYNAMIC
RELATIONSHIPS, THE CASE OF ACETYLCHOLINE BINDING PROTEINS 81
ANTONI R. BLAAZER AND
IWAN J. P.
DE ESCH
5.1 INTRODUCTION 81
5.1.1 NATURAL NACHR LIGANDS 82
5.1.2 NACHR LIGANDS AS THERAPEUTIC AGENTS 83
5.2 ACETYLCHOLINE BINDING PROTEINS (ACHBPS) 85
5.3 THERMODYNAMICS OF SMALL MOLECULE BINDING AT ACHBPS 89
5.3.1 THERMODYNAMICS OF NATURAL PRODUCTS BINDING 90
5.3.2 THERMODYNAMICS OF FRAGMENT GROWING 94
5.4 CONCLUDING REMARKS AND OUTLOOK 98
REFERENCES 99
6 THERMODYNAMICS IN LEAD OPTIMIZATION 107
GEOFFREY A. HOLDGATE, ANDREW SCOTT,
AND GARETH DAVIES
6.1 INTRODUCTION TO LEAD OPTIMIZATION IN DRUG DISCOVERY 107
6.2 MEASUREMENT OF THERMODYNAMIC PARAMETERS IN LEAD
OPTIMIZATION 111
6.2.1 MEASUREMENTS OF ENTHALPY 112
6.2.2 COMPETITION EXPERIMENTS TO DETERMINE AFFINITIES AND ENTHALPIES
FOR TIGHT BINDING COMPOUNDS 112
CONTENTS I VII
6.2.3 INDIRECT MEASUREMENT OF ENTHALPY USING VAN'T HOFF ANALYSIS 113
6.2.4 MEASUREMENT OF K
D
S USING PROTEIN THERMAL UNFOLDING 114
6.2.5 ESTIMATION OF AC
P
OF LIGAND BINDING 116
6.3 ADVANTAGES DURING LEAD OPTIMIZATION FOR THERMODYNAMIC
MEASUREMENTS 117
6.4 EXPLOITATION OF MEASURED THERMODYNAMICS IN LEAD
OPTIMIZATION 118
6.4.1 ENTHALPIC CONSIDERATIONS 119
6.4.2 ENTROPIC CONSIDERATIONS 120
6.5 LEAD OPTIMIZATION BEYOND AFFINITY 120
6.5.1 SELECTIVITY 120
6.5.2 DRUG RESISTANCE 122
6.5.3 MECHANISM OF ACTION 122
6.6 EXEMPLARY CASE STUDIES 123
6.6.1 RENIN 123
6.6.2 CARBONIC ANHYDRASE 124
6.6.3 HMG-COA REDUCTASE 12S
6.6.4 HIV-1 PROTEASE 125
6.6.5 HSP90 126
6.7 POTENTIAL COMPLICATING FACTORS IN EXPLOITING THERMODYNAMICS
IN LEAD OPTIMIZATION 126
6.7.1 PROTEIN FLEXIBILITY AND DYNAMICS 126
6.7.2 THE ROLE OF WATER 127
6.7.3 LINKED EQUILIBRIA 128
6.7.4 ENTHALPY-ENTROPY COMPENSATION 129
6.7.5 ENTROPY-ENTHALPY TRANSDUCTION 131
6.8 SUMMARY 132
REFERENCES 133
7 THERMODYNAMIC PROFILING OF CARBONIC ANHYDRASE INHIBITORS 137
LYN H. JONES
7.1 INTRODUCTION 137
7.2 THERMODYNAMIC PROFILES OF FRAGMENT INHIBITORS 139
7.3 THERMODYNAMICS OF FRAGMENT GROWING 146
7.4 CONCLUSIONS 147
ACKNOWLEDGMENTS 148
REFERENCES 149
SECTION II: KINETICS IS 5
8 DRUG-TARGET RESIDENCE TIME 157
ROBERT A. COPELAND
8.1 INTRODUCTION 157
8.2 OPEN AND CLOSED SYSTEMS IN BIOLOGY 157
VIII CONTENTS
8.3 MECHANISMS OF DRUG-TARGET INTERACTIONS 159
8.4 IMPACT OF RESIDENCE TIME ON CELLULAR ACTIVITY 161
8.5 IMPACT ON EFFICACY AND DURATION IN VIVO 163
8.6 LIMITATIONS OF DRUG-TARGET RESIDENCE TIME 166
8.7 SUMMARY 167
REFERENCES 167
9 EXPERIMENTAL METHODS TO DETERMINE BINDING KINETICS 169
GEORGES VAUQUELIN,
WALTER HUBER,
AND DAVID C. SWINNEY
9.1 INTRODUCTION 169
9.2 DEFINITIONS 170
9.3 EXPERIMENTAL STRATEGY 171
9.4 EXPERIMENTAL METHODOLOGIES 172
9.4.1 RADIOLIGAND BINDING 172
9.4.1.1 KINETIC BINDING PROPERTIES OF THE RADIOLIGAND 172
9.4.1.2 KINETIC BINDING PROPERTIES OF THE UNLABELED DRUGS 173
9.4.1.3 PROS AND CONS OF RADIOLABELED BINDING 2 75
9.4.2 LABEL FREE-SPR 176
9.4.2.1 GENERAL PRINCIPLE OF DATA ACQUISITION 176
9.4.2.2 KINETIC PROFILES FOR BINDING TO IMMOBILIZED ENZYME 177
9.4.2.3 APPLICATIONS OF SPR TO UNRAVEL THE KINETICS OF MOLECULAR
INTERACTIONS 178
9.4.2.4 ADVANTAGES OF USING SPR FOR KINETIC MEASUREMENTS 179
9.4.2.5 DISADVANTAGES OF USING SPR FOR KINETIC MEASUREMENTS 179
9.4.3 SLOW-BINDING KINETICS FROM ENZYME PROGRESS CURVES 180
9.4.3.1 JUMP DILUTION EXPERIMENTS 182
9.4.3.2 PROS OF MEASURING BINDING KINETICS USING ENZYME ACTIVITY 182
9.4.3.3 CONS OF MEASURING BINDING KINETICS USING ENZYME ACTIVITY 183
9.5 SPECIFIC ISSUES 183
9.5.1 HEMI-EQUILIBRIUM CONDITIONS 183
9.5.2 REBINDING 183
9.6 CONCLUSION 185
ACKNOWLEDGMENT 185
REFERENCES 185
10 CHALLENGES IN THE MEDICINAL CHEMICAL OPTIMIZATION OF BINDING
KINETICS 191
MICHAEL J. WARING, ANDREW G. LEACH, AND
DUNCAN C. MILLER
10.1 INTRODUCTION 191
10.2 CHALLENGES 192
10.2.1 ASSAYS AND SCREENING CASCADE 192
10.2.2 MOLECULAR UNDERSTANDING 193
10.2.3 TIMESCALES 197
10.2.4 MOLECULAR PROPERTIES 198
10.3 OPTIMIZATION IN PRACTICE 199
CONTENTS | IX
10.4 SUMMARY AND CONCLUSIONS 208
REFERENCES 209
11 COMPUTATIONAL APPROACHES FOR STUDYING DRUG BINDING KINETICS 211
JULIA
ROMANOWSKA,
DARIA B. KOKH,
JONATHAN C. FULLER, AND
REBECCA C. WADE
11.1 INTRODUCTION 211
11.2 THEORETICAL BACKGROUND 211
11.2.1 KINETICS OF FORMATION OF THE DIFFUSIONAL ENCOUNTER COMPLEX 213
11.2.2 ACCOUNTING FOR MOLECULAR FLEXIBILITY DURING DIFFUSIONAL
ASSOCIATION 214
11.2.3 MODELING AND SIMULATING THE FULL-BINDING PROCESS 216
11.2.3.1 UNBIASED METHODS 216
11.2.3.2 BIASED METHODS 217
11.2.4 COMPUTING KINETIC RATE CONSTANTS FROM FREE ENERGY PROFILES 218
11.3 MODEL TYPES AND FORCE FIELDS 218
11.3.1 ALL-ATOM FORCE FIELDS FOR PROTEINS AND DRUGS 219
11.3.2 EXPLICIT WATER MODELS 220
11.3.3 IMPLICIT SOLVENT FOR ALL-ATOM SOLUTE REPRESENTATION 220
11.3.4 COARSE-GRAIN MODELS 221
11.3.5 HYBRID FORCE FIELD MODELS 222
11.4 APPLICATION EXAMPLES 222
11.4.1 UNBIASED MOLECULAR DYNAMICS SIMULATIONS 222
11.4.1.1 UNDERSTANDING THE BINDING PROCESS: P
2
AR 223
11.4.1.2 CALCULATION OF FC
ON
VALUES: SRC KINASE 224
11.4.1.3 CALCULATION OF K
O{(
VALUES: FK506-BINDING PROTEIN 224
11.4.2 ENHANCED SAMPLING MOLECULAR DYNAMICS TECHNIQUES 224
11.4.2.1 CALCULATION OF K
ON
AND K
OFF
VALUES: HIV-1 PROTEASE INHIBITORS 224
11.4.2.2 RELATING BINDING MODE TO RESIDENCE TIME: COX-1, COX-2 225
11.4.2.3 UNDERSTANDING THE BINDING PROCESS: |3
2
AR AND THE RETINOIC ACID
RECEPTOR 225
11.4.3 BROWNIAN DYNAMICS 225
11.4.3.1 CALCULATION OF K
ON
VALUES: INFLUENZA N1 NEURAMINIDASE 226
11.4.3.2 RESIDENCE TIMES OF ENCOUNTER COMPLEXES: HSP90 AND MDM2 226
11.4.3.3 GATING-TYPE REACTIONS: HIV-1 PROTEASE 227
11.4.4 TOWARD STRUCTURE-KINETIC RELATIONSHIPS (SKRS) 227
11.5 SUMMARY AND FUTURE DIRECTIONS 228
ACKNOWLEDGMENTS 228
REFERENCES 229
12 THE USE
OF STRUCTURAL INFORMATION TO UNDERSTAND BINDING
KINETICS 237
FELIX SCHIELE,
PELIN AYAZ,
AND ANKE
MULLER-FAHRNOW
12.1 INTRODUCTION 237
12.2 BINDING KINETICS 238
X
I
CONTENTS
12.3 METHODS TO OBTAIN STRUCTURAL INFORMATION TO UNDERSTAND BINDING
KINETICS 241
12.3.1 INDIRECT METHODS TO IDENTIFY STRUCTURAL ELEMENTS THAT INFLUENCE
THE
BINDING KINETICS 241
12.3.2 DIRECT METHODS TO CAPTURE STRUCTURAL INFORMATION OF THE
TRANSITION
STATE 242
12.3.3 SIMULATION METHODS 242
12.4 LITERATURE ON STRUCTURE KINETIC RELATIONSHIPS 242
12.4.1 SKR STUDIES 243
12.4.2 INTEGRATION OF MOLECULAR MODELING 248
12.4.3 MOLECULAR FEATURES INFLUENCE KINETICS 249
12.5 CURRENT THINKING ON THE STRUCTURAL FACTORS THAT INFLUENCE BINDING
KINETICS 251
12.6 CONCLUDING REMARKS 252
REFERENCES 253
13 IMPORTANCE OF DRUG-TARGET RESIDENCE TIME AT G PROTEIN-COUPLED
RECEPTORS - A CASE
FOR THE ADENOSINE RECEPTORS 257
DONG
GUO,
ADRIAAN P. UZERMAN,
AND LAURA H. HEITMAN
13.1 INTRODUCTION 257
13.2 THE ADENOSINE RECEPTORS 257
13.3 MATHEMATICAL DEFINITIONS OF DRUG-TARGET RESIDENCE TIME 258
13.4 CURRENT KINETIC RADIOLIGAND ASSAYS 260
13.5 DUAL-POINT COMPETITION ASSOCIATION ASSAY: A FAST AND
HIGH-THROUGHPUT KINETIC SCREENING METHOD 261
13.5.1 PRINCIPLE 261
13.5.2 CASE STUDY 1: THE APPLICATION NOTE OF THE DUAL-POINT COMPETITION
ASSOCIATION ASSAY AT THE A
T
R 263
13.5.3 ADVANTAGES OF THE DUAL-POINT COMPETITION ASSOCIATION ASSAY AND
ITS
FUTURE APPLICATION IN KINETIC BINDING SCREENING 267
13.6 DRUG-TARGET RESIDENCE TIME: AN OFTEN OVERLOOKED KEY ASPECT FOR A
DRUG'S MECHANISM OF ACTION 267
13.6.1 CASE STUDY 2: FUNCTIONAL EFFICACY OF ADENOSINE A
2A
RECEPTOR
AGONISTS IS POSITIVELY CORRELATED TO THEIR RECEPTOR RESIDENCE
TIME 268
13.7 CONCLUSIONS 270
ACKNOWLEDGMENTS 271
REFERENCES 271
14 CASE STUDY:
ANGIOTENSIN RECEPTOR BLOCKERS (ARBS) 273
GEORGES VAUQUELIN
14.1 INTRODUCTION 273
14.2 INSURMOUNTABLE ANTAGONISM 275
14.2.1 INSURMOUNTABLE VERSUS SURMOUNTABLE 275
CONTENTS I XI
14.2.2 ALLOSTERIC VERSUS KINETIC MECHANISMS 275
14.2.3 MEASUREMENT OF DISSOCIATION RATES 278
14.3 FROM PARTIAL INSURMOUNTABILITY TO AN INDUCED FIT-BINDING
MECHANISM 280
14.3.1 PARTIAL INSURMOUNTABILITY 280
14.3.2 THE "INDUCED FIT" BINDING MODEL 281
14.3.3 INSURMOUNTABILITY AND SARTAN STRUCTURE 282
14.3.4 RECEPTOR MUTAGENESIS AND MOLECULAR MODELING 283
14.4 SARTAN REBINDING CONTRIBUTES TO LONG-LASTING ATJ -RECEPTOR
BLOCKADE 283
14.4.1 PHARMACOKINETIC CONSIDERATIONS 283
14.4.2 RADIOLIGAND DISSOCIATION KINETICS AND REBINDING 284
14.4.3 EQUATIONS FOR REBINDING 286
14.4.4 REBINDING VERSUS ALLOSTERIC MODULATION 286
14.5 SUMMARY AND FINAL CONSIDERATIONS 287
REFERENCES 288
15 THE KINETICS
AND THERMODYNAMICS OF STAPHYLOCOCCUS AUREUS FABL
INHIBITION 295
ANDREW CHANG,
KANISHK KAPILASHRAMI, ELEANOR K. H.
ALLEN,
AND PETER
J. TONGE
15.1 INTRODUCTION 295
15.2 FATTY ACID BIOSYNTHESIS AS A NOVEL ANTIBACTERIAL TARGET 296
15.3 INHIBITION OF SAFABL 297
15.4 COMPUTER-AIDED ENZYME KINETICS TO CHARACTERIZE SAFABL
INHIBITION 298
15.5 ORTHOGONAL METHODS TO MEASURE DRUG-TARGET RESIDENCE
TIME 298
15.6 MECHANISM-DEPENDENT SLOW-BINDING KINETICS 303
15.7 MECHANISTIC BASIS FOR BINARY COMPLEX SELECTIVITY 303
15.8 RATIONAL DESIGN OF LONG RESIDENCE TIME INHIBITION 304
15.9 SUMMARY 306
REFERENCES 307
SECTION III: PERSPECTIVE 313
16 THERMODYNAMICS AND BINDING KINETICS
IN DRUG DISCOVERY 315
GYORGY M. KESERU AND DAVID
C. SWINNEY
16.1 INTRODUCTION 315
16.2 REACTION COORDINATE 316
16.3 COMPETING RATES 317
16.4 THERMODYNAMIC CONTROLLED PROCESS - COMPETING RATES UNDER
EQUILIBRIUM CONDITIONS 317
16.5 KINETICS CONTROLLED PROCESSES - COMPETING RATES UNDER
NON-EQUILIBRIUM CONDITIONS 318
CONFORMATIONAL CONTROLLED PROCESS - KINETICS AS A DIAGNOSTIC FOR
CONFORMATIONAL CHANGE 319
THE VALUE OF THERMODYNAMICS MEASUREMENTS TO DRUG
DISCOVERY 320
COMPLEMENTARITY OF BINDING KINETICS AND THERMODYNAMIC TO
DISCOVER SAFER MEDICINES 327
REFERENCES 328
INDEX 331 |
| any_adam_object | 1 |
| author2 | Keserü, György M. |
| author2_role | edt |
| author2_variant | g m k gm gmk |
| author_facet | Keserü, György M. |
| building | Verbundindex |
| bvnumber | BV042506976 |
| classification_rvk | VE 5800 VS 5900 |
| ctrlnum | (OCoLC)910935039 (DE-599)DNB1059940248 |
| dewey-full | 540 615.19 |
| dewey-hundreds | 500 - Natural sciences and mathematics 600 - Technology (Applied sciences) |
| dewey-ones | 540 - Chemistry and allied sciences 615 - Pharmacology and therapeutics |
| dewey-raw | 540 615.19 |
| dewey-search | 540 615.19 |
| dewey-sort | 3540 |
| dewey-tens | 540 - Chemistry and allied sciences 610 - Medicine and health |
| discipline | Chemie / Pharmazie Medizin |
| format | Book |
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| genre | (DE-588)4143413-4 Aufsatzsammlung gnd-content |
| genre_facet | Aufsatzsammlung |
| id | DE-604.BV042506976 |
| illustrated | Illustrated |
| indexdate | 2024-08-03T02:19:06Z |
| institution | BVB |
| isbn | 9783527335824 9783527673049 9783527673056 9783527673032 9783527673025 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-027941571 |
| oclc_num | 910935039 |
| open_access_boolean | |
| owner | DE-20 DE-19 DE-BY-UBM DE-355 DE-BY-UBR DE-703 |
| owner_facet | DE-20 DE-19 DE-BY-UBM DE-355 DE-BY-UBR DE-703 |
| physical | XXIII, 334 S. Ill., graph. Darst. 240 mm x 170 mm |
| publishDate | 2015 |
| publishDateSearch | 2015 |
| publishDateSort | 2015 |
| publisher | Wiley-VCH |
| record_format | marc |
| series | Methods and principles in medicinal chemistry |
| series2 | Methods and principles in medicinal chemistry |
| spelling | Thermodynamics and kinetics of drug binding ed. by György M. Keserü ... 201505 Weinheim Wiley-VCH 2015 XXIII, 334 S. Ill., graph. Darst. 240 mm x 170 mm txt rdacontent n rdamedia nc rdacarrier Methods and principles in medicinal chemistry 65 Wirkstoff-Rezeptor-Bindung (DE-588)4190019-4 gnd rswk-swf Reaktionskinetik (DE-588)4048655-2 gnd rswk-swf Thermodynamik (DE-588)4059827-5 gnd rswk-swf Arzneimittelwechselwirkung (DE-588)4003147-0 gnd rswk-swf Zellrezeptor (DE-588)4133853-4 gnd rswk-swf Arzneimittel (DE-588)4003115-9 gnd rswk-swf Biochemie (DE-588)4006777-4 gnd rswk-swf Rezeptor (DE-588)4049722-7 gnd rswk-swf Ligand Biochemie (DE-588)4606532-5 gnd rswk-swf Physikalische Chemie Rezeptor Wirkstoffforschung TN000 (DE-588)4143413-4 Aufsatzsammlung gnd-content Wirkstoff-Rezeptor-Bindung (DE-588)4190019-4 s Thermodynamik (DE-588)4059827-5 s Reaktionskinetik (DE-588)4048655-2 s DE-604 Rezeptor (DE-588)4049722-7 s Arzneimittelwechselwirkung (DE-588)4003147-0 s Biochemie (DE-588)4006777-4 s Arzneimittel (DE-588)4003115-9 s Zellrezeptor (DE-588)4133853-4 s Ligand Biochemie (DE-588)4606532-5 s Keserü, György M. edt Erscheint auch als Online-Ausgabe Thermodynamics and Kinetics of Drug Binding Methods and principles in medicinal chemistry 65 (DE-604)BV035418617 65 X:MVB text/html http://deposit.dnb.de/cgi-bin/dokserv?id=4809104&prov=M&dok_var=1&dok_ext=htm Inhaltstext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027941571&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Thermodynamics and kinetics of drug binding Methods and principles in medicinal chemistry Wirkstoff-Rezeptor-Bindung (DE-588)4190019-4 gnd Reaktionskinetik (DE-588)4048655-2 gnd Thermodynamik (DE-588)4059827-5 gnd Arzneimittelwechselwirkung (DE-588)4003147-0 gnd Zellrezeptor (DE-588)4133853-4 gnd Arzneimittel (DE-588)4003115-9 gnd Biochemie (DE-588)4006777-4 gnd Rezeptor (DE-588)4049722-7 gnd Ligand Biochemie (DE-588)4606532-5 gnd |
| subject_GND | (DE-588)4190019-4 (DE-588)4048655-2 (DE-588)4059827-5 (DE-588)4003147-0 (DE-588)4133853-4 (DE-588)4003115-9 (DE-588)4006777-4 (DE-588)4049722-7 (DE-588)4606532-5 (DE-588)4143413-4 |
| title | Thermodynamics and kinetics of drug binding |
| title_auth | Thermodynamics and kinetics of drug binding |
| title_exact_search | Thermodynamics and kinetics of drug binding |
| title_full | Thermodynamics and kinetics of drug binding ed. by György M. Keserü ... |
| title_fullStr | Thermodynamics and kinetics of drug binding ed. by György M. Keserü ... |
| title_full_unstemmed | Thermodynamics and kinetics of drug binding ed. by György M. Keserü ... |
| title_short | Thermodynamics and kinetics of drug binding |
| title_sort | thermodynamics and kinetics of drug binding |
| topic | Wirkstoff-Rezeptor-Bindung (DE-588)4190019-4 gnd Reaktionskinetik (DE-588)4048655-2 gnd Thermodynamik (DE-588)4059827-5 gnd Arzneimittelwechselwirkung (DE-588)4003147-0 gnd Zellrezeptor (DE-588)4133853-4 gnd Arzneimittel (DE-588)4003115-9 gnd Biochemie (DE-588)4006777-4 gnd Rezeptor (DE-588)4049722-7 gnd Ligand Biochemie (DE-588)4606532-5 gnd |
| topic_facet | Wirkstoff-Rezeptor-Bindung Reaktionskinetik Thermodynamik Arzneimittelwechselwirkung Zellrezeptor Arzneimittel Biochemie Rezeptor Ligand Biochemie Aufsatzsammlung |
| url | http://deposit.dnb.de/cgi-bin/dokserv?id=4809104&prov=M&dok_var=1&dok_ext=htm http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027941571&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV035418617 |
| work_keys_str_mv | AT keserugyorgym thermodynamicsandkineticsofdrugbinding |