Enzymes and Drugs E-Book

Serge Kirkiacharian

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 245

Veröffentlichungsjahr: 2024

Beschreibung

Enzyme dysfunction, an essential catalyst for the smooth running of biochemical reactions and the maintenance of vital processes, is at the root of many pathologies that have paved the way for the development of numerous drugs.

Aimed at pharmacists, biologists, biochemists, doctors, veterinarians, medicinal chemists and students from a wide range of disciplines, Enzymes and Drugs brings together, for the first time, extensive documentation highlighting the relationships between a large number of drugs and enzymes. The book also highlights new prospects for therapeutic discoveries offered by enzyme targeting.

Numerous applications have been developed thanks to strategies for studying enzyme inhibition or activation, as well as the development of allosteric effectors, presented with their advantages and disadvantages. Various rare diseases, known as "orphan" diseases, have resulted from enzyme deficiency or absence. For their treatment, the introduction of substitute enzymes has led to major therapeutic advances.

Leseprobe

Enzymes and Drugs

Serge Kirkiacharian

Julien Dumond

First published 2024 in Great Britain and the United States by ISTE Ltd and John Wiley & Sons, Inc.

Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms and licenses issued by the CLA. Enquiries concerning reproduction outside these terms should be sent to the publishers at the undermentioned address:

ISTE Ltd27-37 St George’s RoadLondon SW19 4EUUK

www.iste.co.uk

John Wiley & Sons, Inc.111 River StreetHoboken, NJ 07030USA

www.wiley.com

© ISTE Ltd 2024The rights of Serge Kirkiacharian and Julien Dumond to be identified as the authors of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act 1988.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s), contributor(s) or editor(s) and do not necessarily reflect the views of ISTE Group.

Library of Congress Control Number: 2024933510

British Library Cataloguing-in-Publication DataA CIP record for this book is available from the British LibraryISBN 978-1-78630-939-6

Preface

The development of new drugs is a multidisciplinary activity. It draws on various fields such as chemistry, physics, computer science and galenics, as well as proteomics, biology, physiology and enzymology, which play a major role.

The objectives of this book are to:

help biochemistry and biology students in the faculties of medicine, pharmacy, veterinary medicine, engineering and medicinal chemistry to gain access to the field of medicinal enzymology;

make up-to-date information on this discipline available to professional biochemists, chemists, biologists, physicians, pharmacists and veterinarians;

provide useful documentation for basic and applied research in pharmaceutical companies, hospitals and universities;

highlight the many therapeutic applications linked to enzymes, with the help of various examples;

foresee the considerable potential of this discipline for the discovery of new drugs with enzyme activators, inhibitors and enzyme substitutes in the case of many rare diseases.

Despite our meticulous attention to the text we have prepared and checked, errors may have occurred. As is customary, the authors and publisher accept no responsibility for any consequences that may result, and thank readers in advance for informing them of any such errors.

March 2024

Introduction

History

Although enzymes have been involved in fermentation processes since late prehistoric times, it was only in the 18th century that the first notions of “pure” enzymology appeared, with the experiments of Lazzaro Spallanzani. In order to investigate whether digestion was more than just a physical process, he performed several protocols to demonstrate the intervention of other biochemical factors. He was unable to qualify these factors, but he had demonstrated that they existed. These included digestion experiments following the ingestion of pierced wooden capsules filled with meat, as well as tests conducted with tubes containing the gastric juices of birds with meat or cereals, placed under the armpits.

Later, in the 1830s, the first enzyme was characterized. Its role was the catalysis of starch into maltose. The term “diastase”, from the Greek diastasis, was first attributed to it and later replaced by “enzyme”, from the German word Enzym, of Greek origin En (“in”) and Zumé (“brewer’s yeast”).

In 1897, the Buchner brothers discovered the enzymes involved in the alcoholic fermentation process, initially in a therapeutic context, and proved that they function under specific in vitro conditions.

In 1922, the protein nature of enzymes was established, and in 1926, urease, the first enzyme, was isolated in its purest form and crystallized by James Sumner.

By the 1940s, hundreds of enzymes had been purified and crystallized. However, the first crystallographic structure of a protein deduced from X-ray diffraction (Kendrew et al. 1958) (which was myoglobin), and the first amino acid sequencing of ribonuclease (White and Anfinsen 1959), were not obtained until some 20 years later.

Enzymes are therefore protein-based biological catalysts. Catalysts are chemical reaction accelerators. Some RNAs may also have catalytic activity (Altman and Cech 1989).

Life depends on structures, within which chemical reactions take place in an orderly manner in time and space (the anabolism and catabolism of living organisms). Without enzymes, chemical reactions would not be compatible with life. Their dysfunction results in the appearance of various pathologies, which are nowadays partially overcome by the development of new drugs thanks to scientific progress in many fields.

Fields of application

Enzymes were first studied for their involvement in the metabolism of living organisms. Initially, these were easily accessible molecules (derived from liquids or simple organisms). When purification processes were improved, many enzymes were isolated. Once characterized, their possible applications by and for humans could be considered. Today, there are three major areas of enzyme targeting and industrial applications:

pharmaceutical and cosmetics companies;

food companies (Kilara and Shahani

1979

);

environment-related companies with a view to generating environmentally friendly products (Baupai

1999

; McKinlay et al.

2007

).

Sometimes, the same product can be used in all three areas (as in the case of succinate or mannan (Zeikus et al. 1999; Singh et al. 2018)). It should also be noted that enzymatic reactions are used to carry out various transformations in organic synthesis and medicinal chemistry. However, this vast field will not be covered in this book. The same applies to enzymatic activity determinations used as a means of clinical diagnosis.

The objectives of this book

The progress made in enzymology since the birth of this science has made it possible to broaden its various fields of application.

The aim of this book is to highlight the importance of enzymes in medicinal chemistry, and to consider present and future strategies to overcome enzymatic deficiencies.

Each enzyme molecule has a well-defined mission within the cell, catalyzing a specific chemical reaction. It is an indispensable part of a whole that goes beyond it, but which desperately needs it. If it does not work, or does not work well enough, or even too well, the organism suffers the consequences. Strategies are then available to correct these transient or permanent failures.

The book is divided into five chapters. The first deals briefly with the catalytic activity of enzymes and the various techniques for studying enzymatic kinetics. Subsequent chapters focus on the role of enzymes in the various therapeutic fields of viruses, bacteria, fungi, protozoa and humans. They cover the following topics:

the mechanism of action of various drugs;

the development of treatments or substitute enzymes to correct their deficiency;

the discovery of new enzyme targets with a view to developing new treatments through the contributions of medicinal chemistry and genetics.

It is worth noting that the pharmaceutical industry uses enzymes to produce intermediates and/or chiral drugs in a single step, offering significant economic and ecological advantages over conventional organic synthesis processes. However, this vast field will not be covered in this book.

References

Altman, S. and Cech, T.R. (1989). Propriétés catalytiques de certains ARN. Nobel Prize in Chemistry [Online]. Available at:

https://www.nobelprize.org/prizes/chemistry/1989/summary/

.

Bajpai, B. (1999). Application of enzymes in the pulp and paper industry.

Biotechnol. Prog.

, 15(2), 147–157.

Kendrew, J.C., Bodo, G., Dintzis, H.M., Parrish, R.G., Wyckoff, H., Phillips, D.C. (1958). A three-dimensional model of the myoglobin molecule obtained by x-ray analysis.

Nature

, 181(4610), 662–666.

Kilara, A. and Shahani, K.M. (1979). The use of immobilized enzymes in the food industry: A review.

CRC Crit. Rev. Food Sci. Nutr.

, 12(2), 161–198.

McKinlay, J.B., Vieille, C., Zeikus, J.G. (2007). Prospects for a bio-based succinate industry.

Appl. Microbiol. Biotechnol.

, 76(4), 727–740.

Singh, S., Singh, G., Arya, S.K. (2018). Mannans: An overview of properties and application in food products.

Int. J. Biol. Macromol.

, 119, 79–95.

White, F.H. and Anfinsen, C.B. (1959). Some relationships of structure to function in ribonuclease.

Ann. N Y Acad. Sci.

, 81, 515–523.

Zeikus, J.G., Jain, M.K., Elankovan, P. (1999). Biotecnology of succinic acid production and markets for derived industria products.

Appl. Environ. Microbiol.

, 51, 545–552.