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Quantum biochemistry and, specific interactions
TIBS--
Variable opiate research meeting Opiates and Endogenous Peptides by H. W. Kosterlitz, Holland Publishing New York/Oxford,
Opioid
published
by North-
Company, Amsterdam/ 1976. DjI.95.- ($36.50)
(x + 456 pages)
This book is the proceedings of the 5th International Narcotics Research Club meeting held last July in Aberdeen and consists of 67 concise papers. Remarkably, the publication date is only two months after the meeting. During the last few years opiate research has moved extremely rapidly and the latest breakthrough, in which a group of peptides that possess opiate-like activity was discovered to be endogenous to the mammalian brain, occurred less than one year ago. The book is dominated by new research into the actions of these peptides, now called generically by the term ‘endorphins’. Most of the known endorphins appear to be fragments of the pituitary peptide blipotropin. The isolation and purification of these peptides are described, and the ability of the endorphins and the classical alkaloid opiates to bind to specific brain opiate receptors is compared. From these binding studies and other data, several authors argue that there may be not only a single species of opiate receptor, but a whole family of opiate receptors that differ in their binding affinities and kinetics. The opiate-like derivatives of /I-lipotropin can be subdivided by size into two classes : the enkephalins, which are pentapeptides, and the much larger (28-30 residues) endorphins, many or all of which contain an enkephalin unit at their N-terminus. A central issue throughout the book is the comparison of pharmacological properties of the enkephalins and larger endorphins. Many authors reported that the larger endorphins are several orders of magnitude more potent than the enkephalins when tested in a variety of binding assays and bioassays. However, the enkephalins are very sensitive to proteolytic digestion and this may explain their low potency. Various other pharmacological properties of these new peptides are described, such as analgesia, behavioural effects and their actions on morphine-sensitive peripheral targets, as well as on adenylate and guanylate cyclases of brain. In all these test systems endorphin activity bears a striking resemblance to that of morphine. A portion of the book is devoted to extracellular electrophysiological studies of the endor-
phins, and in general these compounds are shown to mimic the actions of morphine. The regional distribution of enkephalin is reported to follow closely that of the opiate receptor, and several authors discuss the possibility that one of the endorphins may act as a neurotransmitter. Much of the book is also devoted to more traditional aspects of narcotic research. As usual, opiate-induced tolerance and dependence receive good coverage although no real insights into these complicated phenomena are presented. This book therefore must be regarded as a progress report on the state of opiate research and although several papers have since been revised and published more fully in scientific journals it is useful to have the most recent research into narcotic action gathered together in one volume. However, those not directly involved in this field and indeed those in the field who missed the meeting will undoubtedly be disappointed by the absence of review papers and of an overview of the debates that occurred in Aberdeen. Several quite heated discussions occurred at the meeting itself and some explanation of the major points of contention must have been worthy of recording for posterity. The prompt publication of this book ensures that it will be valued for the next few years as an unusually up-to-date reference source to the opiates and an essential companion for authors of both reviews and applications for funding. It is not suitable for teaching purposes since no overviews of the subject are included. Indeed, it may be difficult for someone not familiar with the field, to obtain a balanced view by our usual technique of flicking through the pages until a familiar name or phrase encourages one to browse. The peptides of opiate research are young and many of the points presented on one page are contested on another. In addition a fairly high proportion of the papers in the volume will be best remembered for their authors ability to present disjointed data in the space allotted by the organizers of the meeting. We cannot avoid the feeling that some authors have seized this book as an opportunity to publish their unfinished work which may be completed later. On the other hand several authors have contributed concise, well-developed papers which must be the fruit of well-nurtured research. This book consists of 456 glossy pages in ‘camera-ready’ format, in a sturdy attractive binding, which is a credit to the publisher. We are tempted to suggest that any other approach to the publication of the proceedings of highly specialised meetings must be obsolete. One must also admire an editor who can persuade his
February
1977
publisher and 67 authors to agree and meet their deadlines. On the other hand, the price of this volume ($36.50) will be regarded by many as excessive. JOHN S. KELLY RAY DINGLEDINE
John S. Kelly and Ray Dingledine are members of the Medical Research Council Staff at the Neurochemical Pharmacology Unit, Department of Pharmacology, Medical School, Cambridge, U.K.
A wealth of fundamental detail Quantum Biochemistry Specific Interactions
and
by Zeno Simon, published by Abacus Press, U.K., 1976. E11.95 (approx. S20.-) (251 pages)
This little but exhaustive book will be interesting and inspiring to those who like to explore and understand biological problems on the fundamental level of electronic and physico-chemical structures and factors. Its lirst three chapters are devoted to the description of the different approximations of the molecular orbital methods and of the theory of intermolecular forces within the context of quantum mechanics and of the empirical procedures. The next two chapters deal with the exploration of the electronic and conformational properties of the essential biological compounds. The last two chapters are devoted to the problems of specific interactions and to a detailed analysis of some recognition processes. The presentation of the different subjects is well documented and the book contains a wealth of useful information. The applicability of the theoretical procedure:, whether quantum mechanical or empirical, is illustrated on numerous examples. One major omission in a book with this title is the lack of any reference to the large amount of quantum-mechanical computations which have been carried out during recent years on the conformational properties of proteins, nucleic acids and their constituents, for which the author reports only the results of some relatively less significant and less efficient empirical computations. Large parts of the book, in particular those related to the analysis oi some recognition processes, present interesting subjects for deeper quantitative investigations. A. PULLMAN
A. Pullman is Director of Research at the Centre
National de la Recherche Scientifique, Paris, France.
Variable opiate research meeting Opiates and Endogenous Peptides by H. W. Kosterlitz, Holland Publishing New York/Oxford,
Opioid
published
by North-
Company, Amsterdam/ 1976. DjI.95.- ($36.50)
(x + 456 pages)
This book is the proceedings of the 5th International Narcotics Research Club meeting held last July in Aberdeen and consists of 67 concise papers. Remarkably, the publication date is only two months after the meeting. During the last few years opiate research has moved extremely rapidly and the latest breakthrough, in which a group of peptides that possess opiate-like activity was discovered to be endogenous to the mammalian brain, occurred less than one year ago. The book is dominated by new research into the actions of these peptides, now called generically by the term ‘endorphins’. Most of the known endorphins appear to be fragments of the pituitary peptide blipotropin. The isolation and purification of these peptides are described, and the ability of the endorphins and the classical alkaloid opiates to bind to specific brain opiate receptors is compared. From these binding studies and other data, several authors argue that there may be not only a single species of opiate receptor, but a whole family of opiate receptors that differ in their binding affinities and kinetics. The opiate-like derivatives of /I-lipotropin can be subdivided by size into two classes : the enkephalins, which are pentapeptides, and the much larger (28-30 residues) endorphins, many or all of which contain an enkephalin unit at their N-terminus. A central issue throughout the book is the comparison of pharmacological properties of the enkephalins and larger endorphins. Many authors reported that the larger endorphins are several orders of magnitude more potent than the enkephalins when tested in a variety of binding assays and bioassays. However, the enkephalins are very sensitive to proteolytic digestion and this may explain their low potency. Various other pharmacological properties of these new peptides are described, such as analgesia, behavioural effects and their actions on morphine-sensitive peripheral targets, as well as on adenylate and guanylate cyclases of brain. In all these test systems endorphin activity bears a striking resemblance to that of morphine. A portion of the book is devoted to extracellular electrophysiological studies of the endor-
phins, and in general these compounds are shown to mimic the actions of morphine. The regional distribution of enkephalin is reported to follow closely that of the opiate receptor, and several authors discuss the possibility that one of the endorphins may act as a neurotransmitter. Much of the book is also devoted to more traditional aspects of narcotic research. As usual, opiate-induced tolerance and dependence receive good coverage although no real insights into these complicated phenomena are presented. This book therefore must be regarded as a progress report on the state of opiate research and although several papers have since been revised and published more fully in scientific journals it is useful to have the most recent research into narcotic action gathered together in one volume. However, those not directly involved in this field and indeed those in the field who missed the meeting will undoubtedly be disappointed by the absence of review papers and of an overview of the debates that occurred in Aberdeen. Several quite heated discussions occurred at the meeting itself and some explanation of the major points of contention must have been worthy of recording for posterity. The prompt publication of this book ensures that it will be valued for the next few years as an unusually up-to-date reference source to the opiates and an essential companion for authors of both reviews and applications for funding. It is not suitable for teaching purposes since no overviews of the subject are included. Indeed, it may be difficult for someone not familiar with the field, to obtain a balanced view by our usual technique of flicking through the pages until a familiar name or phrase encourages one to browse. The peptides of opiate research are young and many of the points presented on one page are contested on another. In addition a fairly high proportion of the papers in the volume will be best remembered for their authors ability to present disjointed data in the space allotted by the organizers of the meeting. We cannot avoid the feeling that some authors have seized this book as an opportunity to publish their unfinished work which may be completed later. On the other hand several authors have contributed concise, well-developed papers which must be the fruit of well-nurtured research. This book consists of 456 glossy pages in ‘camera-ready’ format, in a sturdy attractive binding, which is a credit to the publisher. We are tempted to suggest that any other approach to the publication of the proceedings of highly specialised meetings must be obsolete. One must also admire an editor who can persuade his
February
1977
publisher and 67 authors to agree and meet their deadlines. On the other hand, the price of this volume ($36.50) will be regarded by many as excessive. JOHN S. KELLY RAY DINGLEDINE
John S. Kelly and Ray Dingledine are members of the Medical Research Council Staff at the Neurochemical Pharmacology Unit, Department of Pharmacology, Medical School, Cambridge, U.K.
A wealth of fundamental detail Quantum Biochemistry Specific Interactions
and
by Zeno Simon, published by Abacus Press, U.K., 1976. E11.95 (approx. S20.-) (251 pages)
This little but exhaustive book will be interesting and inspiring to those who like to explore and understand biological problems on the fundamental level of electronic and physico-chemical structures and factors. Its lirst three chapters are devoted to the description of the different approximations of the molecular orbital methods and of the theory of intermolecular forces within the context of quantum mechanics and of the empirical procedures. The next two chapters deal with the exploration of the electronic and conformational properties of the essential biological compounds. The last two chapters are devoted to the problems of specific interactions and to a detailed analysis of some recognition processes. The presentation of the different subjects is well documented and the book contains a wealth of useful information. The applicability of the theoretical procedure:, whether quantum mechanical or empirical, is illustrated on numerous examples. One major omission in a book with this title is the lack of any reference to the large amount of quantum-mechanical computations which have been carried out during recent years on the conformational properties of proteins, nucleic acids and their constituents, for which the author reports only the results of some relatively less significant and less efficient empirical computations. Large parts of the book, in particular those related to the analysis oi some recognition processes, present interesting subjects for deeper quantitative investigations. A. PULLMAN
A. Pullman is Director of Research at the Centre
National de la Recherche Scientifique, Paris, France.