Mechanism of Action of Antieukaryotic and Antiviral Compounds


Book Description

When Antibiotics I was published in 1967, the teleological view was held by some that" antibiotics" were substances elaborated by certain microorgan isms for the purpose of competing with other microorganisms for survival in mixed ecological environments. However, not only had J. EHRLICH and his associates shown 15 years earlier that chloramphenicol was produced by Strepto myces venezuelae in cultures of sterilized soils but not in parallel cultures of the same soils which were not sterilized, but operationally, the search for anti cancer antibiotics was actively under way (Antibiotics I reporting on numerous such substances), although the concept of antibiosis could not logically justify such undertakings. This editor hesitates to accept the use of the term "antibiotic" for anti microbial agents of non microbiological origins which is sometimes encountered, but neither does he subscribe to the view that antibiotics are in some fundamental manner different from chemotherapeutic substances of other origins. Modes and mechanisms of action of chemotherapeutic compounds are not systematic functions of their origins nor of the taxonomical position of the target organisms. Consequently, in the selection of topics for Antibiotics III (published in 1975), synthetic drugs and natural products of higher plants (alkaloids) were represented, along with antibiotics in the strict sense of the definition. We now present Antibiotics V, for whose assembly the same selection criteria were applied as for Antibiotics Ill. The aggregate length of the contributions rendered it impractical to place the entire text between the covers of one book.




Mechanism of Action of Antibacterial Agents


Book Description

The first volume of Antibiotics was published in 1967 and contained a series of review papers on antibiotic actions. The editors, Drs. GOTTLIEB and SHAW, were aware of the rapid development of this field of study and provided a number of addenda in an effort to keep knowledge up to date while the book was in production. One year after the publication of Antibiotics I, this editor had a conference with Dr. KONRAD F. SPRINGER in which it became clear that another volume on actions of antibiotics would be necessary. For a variety of reasons, this was delayed until 1975 and became Antibiotics III. It did not contain addenda since it was recognized by the editors, Drs. CORCORAN and HAHN, that still another volume would have to follow and that in a moving field, such as the study of the actions of antibacterial drugs, no publication can be definitive or remain current, except for a limited period of time. The editors of Volume III grouped the contributions into sections: 1. Inter ference with nucleic acid biosyntheses, 2. Interference with protein biosynthesis, and 3. Interference with cell wall/membrane biosynthesis, specific enzyme sys tems, and those in which the mode of action was not known with certainty.




Biosynthesis


Book Description

The Series on Antibiotics produced by Springer-Verlag began more than a decade ago with the nearly simultaneous appearance of two volumes, one dealing with the mode of action of antibiotics and the other concerning the biosynthesis of them. The standards set by the original Editors were high, and these books have proved useful to many. The rapid advances in our knowl edge of the mode of action of antibiotics and other antitumor agents has stimu lated two further works in the same series (Volume III, 1975; and Volumes Vj1 and Vj2, 1979). For some time it had appeared to Dr. Konrad Springer that the time might' be ripe' for bringing the subject of the biosynthesis of antibiotics up-to-date. This Editor agreed to survey the literature and discuss this possibility with his colleagues who are active in research on antibiotics. In spite of the appearance of numerous review articles, both of a highly special ized and general nature, on the biosynthesis of antibiotics, it was agreed generally that it would be extremely useful to add a new volume on biosynthesis to the Series. Such a work should focus on collecting a group of contributions dealing with those antibiotics whose biosynthesis is understood in much greater detail now than it was in the middle 1960's. Since Volume II on biosynthesis continues to be available, this addition to the series has not dealt with each and every antibiotic whose biosynthesis was studied long ago.




Nucleic Acids and Proteins in Plants II


Book Description

With contributions by numerous experts




Modes and Mechanisms of Microbial Growth Inhibitors


Book Description

It is not certain that the editors of Antibiotics I (1967), Drs. GOTTLffiB and SHAW, fully realized that they were laying the foundation for an entire series of which we present here Vol. VI. For some time to come, this will be the last volume of the Antibiotics series. There are several reasons for this. Firstly, the discovery of medicinally useful antibiotics has leveled off, because the number of microbiological products with antimicrobial properties is not infinite. In 1972 some 2500 antibiotic substances were known, of which approximately one per cent are clinically useful. Further search for antibiotics has led to increasing frequency of rediscoveries and drasti cally decreasing frequency of discoveries of new antibiotics. As the search for antibiotics with a standard methodology in conventional ecological niches has exhausted itself, there is a paucity of new and interesting substances on which to undertake modes/mechanisms of action studies. Secondly, the mechanism of action field has come of age and its results are now academic knowledge. This also holds true for synthetic chemothera peutic drugs and becomes the case rapidly for toxic substances with anti-eukar yotic action. The study of mechanisms of action was undertaken for two reasons: one was the basic scientific desire to know how antimicrobial substances inter fered with microbial biochemistry; the second one was the hope that such infor mation would be useful in the premeditated design of synthetic antimicrobials.




Mechanism of Action of Antibacterial Agents


Book Description

The first volume of Antibiotics was published in 1967 and contained a series of review papers on antibiotic actions. The editors, Drs. GOTTLIEB and SHAW, were aware of the rapid development of this field of study and provided a number of addenda in an effort to keep knowledge up to date while the book was in production. One year after the publication of Antibiotics I, this editor had a conference with Dr. KONRAD F. SPRINGER in which it became clear that another volume on actions of antibiotics would be necessary. For a variety of reasons, this was delayed until 1975 and became Antibiotics III. It did not contain addenda since it was recognized by the editors, Drs. CORCORAN and HAHN, that still another volume would have to follow and that in a moving field, such as the study of the actions of antibacterial drugs, no publication can be definitive or remain current, except for a limited period of time. The editors of Volume III grouped the contributions into sections: 1. Inter ference with nucleic acid biosyntheses, 2. Interference with protein biosynthesis, and 3. Interference with cell wall/membrane biosynthesis, specific enzyme sys tems, and those in which the mode of action was not known with certainty.







Structural and Functional Aspects of Enzyme Catalysis


Book Description

Enzymes perform the executive role in growth, energy conversion, and repair of a living organism. Their activity is adjusted to their en vironment within the cell, being turned off, switched on, or finely tuned by specific metabolites according to demands at the physiologi cal level. Each enzyme discovered in the long history of enzymology has revealed its own individuality. Even closely related members of a family differ in specificity, stability or regulatory properties. Despite these, at first sight overwhelming aspects of individuality, common factors of enzymic reactions have been recognized. Enzymes are stereospecific catalysts even when a nonspecific process would yield the same product. Knowledge of the detailed stereochemistry of an enzymic reaction helps to deduce reaction mechanisms and to ob tain insight into the specific binding of substrates at the active site. This binding close to catalytically competent groups is related to the enormous speed of enzyme-catalyzed reactions. The physical ba sis of rate-enhancement is understood in principle and further exploit ed in the design of small organic receptor molecules as model enzymes. These aspects of enzyme catalysis are discussed in Session 1. Session 2 emphasizes the dynamic aspects of enzyme substrate inter action. Substrate must diffuse from solution space to the enzyme's surface. This process is influenced and can be greatly facilitated by certain electrostatic propterties of enzymes. The dynamic events during catalysis are studied by relaxation kinetics or NMR techniques.




Dictionary of Antibiotics and Related Substances


Book Description

Bacterial and parasitic diseases are the second leading cause of death worldwide, according to a report by the London School of Economics. Due to the emergence of drug-resistant "superbugs," like methicillin-resistant Staphylococcus aureus (MRSA), traditional antibiotics such as penicillin and its derivatives are in danger of becoming obsolete. In




Chemotherapy of Viral Infections


Book Description

" . . . the motto for the therapeutics of the future will have to be de sedibus et causis pharmacorum. " P. EHRLICH, 1909 Exciting events in the basic disciplines of virology, immunology, and pharmacology continue to advance the understanding of the pathogenesis and control of virus diseases. At the same time, the rational development of antiviral agents is attracting, to an increasing extent, the interest of workers in other disciplines. Improvements in technology facilitate the definition of potential target sites for antiviral intervention and unmask new viral and host genes. The outcome is a further steady development of new antiviral agents which approach the "magic bullets" first proposed by PAUL EHRLICH. Remarkable advances in protein synthetic methods that yield polypeptides which inhibit active sites of viral proteins have aided substantially in the basic and clinical study of these antiviral agents. In addition, the extremely rapid progression in recombinant DNA techniques, leading to the synthesis of large quantities of gene products, is also increasing our opportunities at a dashing pace. New information and developing technology facilitate research on the mechanism of action, toxicity, pharmacokinetics, and pharmacodynamics of new agents. The list of clinically effective antiviral agents is expanding and the number of potentially useful compounds is growing rapidly. This book is a combined theoretical text and practical manual which, it is hoped, will be of use to all who have an interest in virus diseases, particularly scientists, physicians and graduate students.