Pharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors, and Enzymes in Health and Diseases

801 Pages·2019·29.359 MB·\801

by  Peter Grunwald (Editor)

Jenny Stanford Series
on Biocatalysis
Volume 4
Pharmaceutical Biocatalysis
Jenny Stanford Series on Biocatalysis
Series Editor
Peter Grunwald
Titles in the Series
Published Forthcoming
Vol. 1 Vol. 5
Industrial Biocatalysis Pharmaceutical Biocatalysis:
Peter Grunwald, ed. Chemoenzymatic Synthesis
2015 of Active Pharmaceutical
978-981-4463-88-1 (Hardcover) Ingredients
978-981-4463-89-8 (eBook) Peter Grunwald, ed.
2019
Vol. 2
Handbook of Carbohydrate- Vol. 6
Modifying Biocatalysts Pharmaceutical Biocatalysis:
Peter Grunwald, ed.
Biotransformations, Novel
2016
Therapeutics, Natural Sources,
978-981-4669-78-8 (Hardcover)
and Degradation
978-981-4669-79-5 (eBook)
Peter Grunwald, ed.
2020
Vol. 3
Biocatalysis and
Nanotechnology
Peter Grunwald, ed.
2017
978-981-4613-69-9 (Hardcover)
978-1-315-19660-2 (eBook)
Vol. 4
Pharmaceutical Biocatalysis:
Fundamentals, Enzyme
Inhibitors, and Enzymes in
Health and Diseases
Peter Grunwald, ed.
2019
978-981-4800-61-7 (Hardcover)
978-0-429-29503-4 (eBook)
Jenny Stanford Series
on Biocatalysis
Volume 4
Pharmaceutical Biocatalysis
Fundamentals, Enzyme Inhibitors, and
Enzymes in Health and Diseases
edited by
Peter Grunwald
Published by
Jenny Stanford Publishing Pte. Ltd.
Level 34, Centennial Tower
3 Temasek Avenue
Singapore 039190

Email: [email protected]
Web: www.jennystanford.com
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Pharmaceutical Biocatalysis: Fundamentals, Enzyme Inhibitors,
and Enzymes in Health and Diseases
Copyright © 2019 Jenny Stanford Publishing Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced in any
form or by any means, electronic or mechanical, including photocopying,
recording or any information storage and retrieval system now known or
to be invented, without written permission from the publisher.
For photocopying of material in this volume, please pay a copying fee
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required from the publisher.
ISBN 978-981-4800-61-7 (Hardcover)
ISBN 978-0-429-29503-4 (eBook)
Contents
Preface
xxi
1. Pharmaceuticals: Some General Aspects 1
Peter Grunwald
1.1 Introduction 1
1.2 General Remarks 2
1.3 Orphan Drugs and Rare Diseases 6
1.4 The World Market of Pharmaceuticals,
Therapeutic Enzymes, and Enzyme Inhibitors 11
1.5 Drug Development Process, Risks, and Costs of
Drug Development, and Prescription Drug Prices 16
1.5.1 Drug Development in Europe and Germany 18
1.5.2 Risks in Drug Development and
Mitigation Strategies 20
1.5.3 Randomized Clinical Trials and Beyond 21
1.5.4 Prescription Drug Prices 23
1.5.4.1 Cost reduction: public–private
drug partnerships 28
2. 1U.s6e ofC Eonnzcylumdeins gin R tehmea Drkosw nstream Processing of 30
Biopharmaceuticals 41
Duarte Miguel F. T. Prazeres
2.1 Introduction 41
2.2 Cell Dissociation and Lysis 44
2.2.1 Cell Dissociation 44
2.2.2 Cell Lysis 48
vi Contents
2.3 Impurity Clearance 49
2.3.1 Nucleic Acid Clearance 50
2.3.2 Protein Clearance 53
2.4 Targeted Structural Modifications 54
2.4.1 Affinity Tag Removal 54
2.4.2 Precursor Maturation 56
2.4.3 Structural Modification of Impurities 58
2.4.4 Glycosylation 59
2.5 Discussion 60
2.5.1 Points to Consider 60
2.5.2 Pros and Cons 62
3. 2Th.6e rapCeountcilcu sUiosen so f Carbonic Anhydrase Inhibitors 63
and Their Multiple Drug Interactions 73
Andrea Angeli and Claudiu T. Supuran
3.1 Introduction 73
3.2 First- and Second-Generation Clinically Used
Sulfonamides and Their Drug Interactions 76
3.3 Sulfonamides with Diuretic Action: Bumetanide,
Hydrochlorothiazide, Furosemide, Indapamide,
and Chlortalidone 79
3.4 Sulfonamides/Sulfamates as Antiepileptic Drugs:
Sulthiame, Topiramate, and Zonisamide 81
3.5 Celecoxib, Valdecoxib, and Polmacoxib as
CA/COX-2 Inhibitors 85
3.6 Inhibitors of Carbonic Anhydrases as Antitumor
Agents 86
3.7 Conclusions and Repurposing Old Drugs for
4. FibrinoNleywti cD Eisnezaysme eAsp fporro Tahcrhoems bolytic Therapy 8999
Swaroop S. Kumar and Sabu Abdulhameed
4.1 Introduction 99
4.2 Status of Anticoagulants and Antiplatelets 102
Contents vii
4.2.1 Heparin and Derivatives 102
4.2.2 Coumarin Derivatives 103
4.2.3 Thrombin Inhibitors 104
4.2.4 Factor Xa Inhibitors 104
4.2.5 Antiplatelet Drugs 105
4.3 Thrombolytic Drugs 106
4.3.1 Plasminogen Activators as Thrombolytic
Drugs 107
4.3.1.1 First-generation plasminogen
activators as thrombolytic drugs 108
4.3.1.2 Second-generation plasminogen
activators 110
4.3.1.3 Third-generation plasminogen
activators (by protein
engineering) 113
4.3.2 Direct-Acting Plasmin-Like Thrombolytic
Drugs 119
4.3.2.1 Non-microbial thrombolytic
enzymes 119
4.3.2.2 Microbial thrombolytic enzymes 127
5. R4.o4l e oCf oEnncgluinseioenre d Proteins as Therapeutic 141
Formulations 159
Khushboo Gulati and Krishna Mohan Poluri
5.1 Introduction 159
5.2 Protein Engineering Approaches 161
5.2.1 Directed Evolution 162
5.2.1.1 Asexual methods 164
5.2.1.2 Sexual methods 165
5.2.2 Computational Designing 167
5.2.2.1 Rational designing 168
5.2.2.2 De novo designing 169
5.2.3 Combinatorial Approach 170
5.3 Protein Therapeutics 175
viii Contents
5.3.1 Antibodies 175
5.3.2 Enzymes as Therapeutics 177
5.3.3 Cytokines and Their Receptors 179
5.3.4 Hormones 181
5.3.5 G-Protein Coupled Receptor Targeting
Antibodies 183
5.3.6 Cardiovascular Therapeutics 184
5.3.7 Coagulation Factors 184
5.4 Protein-Based Scaffolds for Therapeutic
Applications 185
5.4.1 Monobodies 186
5.4.2 SH3 Domains/Fynomers 186
5.4.3 Lipocalins/Anticalins 187
5.4.4 Nanobodies/VHH Domains 188
5.4.5 DARPins 188
5.4.6 Affibodies 189
5.4.7 Avimers 190
5.4.8 Knottins and Cyclotides 190
5.4.9 Kringle Domain 191
5.4.10 Kunitz Domain 192
6. 5Sy.5n theCsoins coluf dBiinoga cRteivmea Prekps tides for Pharmaceutical 192
Applications 205
Jaison Jeevanandam, Ashish Kumar Solanki, Shailza Sharma,
Prabir Kumar Kulabhusan, Sapna Pahil, and Michael K. Danquah
6.1 Introduction 205
6.2 Synthesis of Bioactive Peptides 207
6.2.1 Chemical Synthesis 207
6.2.1.1 Synthesis in solution 207
6.2.1.2 Solid-phase peptide synthesis 209
6.2.1.3 Sequential condensation of
solid phase fragments 210
6.2.2 Enzymatic Synthesis 210
Contents ix
6.2.2.1 Classification of proteolytic
enzymes used for peptide
synthesis 211
6.2.3 rDNA Technology 213
6.2.3.1 Fusion expression 213
6.2.3.2 Direct expression 213
6.2.4 Other Novel Peptide Synthesis Methods 214
6.2.4.1 Utilizing microwave energy for
peptide production 215
6.2.4.2 Ligation 215
6.2.4.3 Recent developments 216
6.3 Purification, Characterization, and
Nanoformulation of Biopeptides 216
6.3.1 Purification 216
6.3.1.1 High-performance liquid
chromatography for
biopeptide purification 218
6.3.1.2 Capillary electrophoresis 221
6.3.1.3 Affinity chromatography 221
6.3.2 Characterization Methods 221
6.3.3 Nanoformulation 224
6.4 Pharmaceutical Application of Bioactive
Peptides 226
6.4.1 Antimicrobial Agent 226
6.4.2 Anticancer Agent 228
6.4.3 Antihypertensive Agent 230
6.4.4 Bioactive Peptides for Skin Disease
Treatments 232
6.4.4.1 Skin infections and biofilms 232
6.4.4.2 Skin cancer and hyper-
pigmentation 233
6.4.4.3 Skin burns 233
6.4.4.4 Diabetic foot ulcers and other
chronic skin wounds 234
6.4.5 Bioactive Peptides as Immuno and
Cytomodulatory Agents 235