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Book
PARP Inhibitors for Cancer Therapy
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ISBN: 9783319141510 3319141503 9783319141503 3319141511 Year: 2015 Publisher: Cham : Springer International Publishing : Imprint: Humana,

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Abstract

PARP Inhibitors for Cancer Therapy provides a comprehensive overview of the role of PARP—poly ADP ribose polymerase—in cancer therapy. The volume covers the history of the discovery of PARP and its role in DNA repair. Additionally, it describes the discovery of the PARP family, and includes a discussion of other DNA maintenance-associated PARPs. As well, the volume features a section on the accessible chemistry behind the development of inhibitors. PARP inhibitors—PARPi—are a group of pharmacological inhibitors that are particularly good targets for cancer therapy. PARP plays a pivotal role in DNA repair and may contribute to the therapeutic resistance to DNA-damaging agents used to treat cancer. Researchers have learned a great deal about the biology of PARP and how tumor-specific defects in DNA repair can be exploited by PARPi. The “synthetic lethality” of PARPi is an exciting concept for cancer therapy, and has led to heightened activity in this area.


Book
Kinetics of Enzyme-Modifier Interactions : Selected Topics in the Theory and Diagnosis of Inhibition and Activation Mechanisms
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ISBN: 9783709114025 3709114012 9783709114018 3709114020 Year: 2015 Publisher: Vienna : Springer Vienna : Imprint: Springer,

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The kinetic mechanisms by which enzymes interact with inhibitors and activators, collectively called modifiers, are scrutinized and ranked taxonomically into autonomous species in a way similar to that used in the biological classification of plants and animals. The systematization of the mechanisms is based on two fundamental characters: the allosteric linkage between substrate and modifier and the factor by which a modifier affects the catalytic constant of the enzyme. Combinations of the physically significant states of these two characters in an ancestor-descendant-like fashion reveal the existence of seventeen modes of interaction that cover the needs of total, partial and fine-tuning modulation of enzyme activity. These interactions comprise five linear and five hyperbolic inhibition mechanisms, five nonessential activation mechanisms and two hybrid species that manifest either hyperbolic inhibition or nonessential activation characteristics depending on substrate concentration. Five essential activation mechanisms, which are taxonomically independent of the mentioned basic species, complete the inventory of enzyme modifiers. Often masked under conventional umbrella terms or treated as anomalous cases, all seventeen basic inhibition and nonessential activation mechanisms are represented in the biochemical and pharmacological literature of this and the past century, either in the form of rapid or slow-onset reversible interactions, or as irreversible modification processes. The full potential of enzyme inhibitors and activators can only be appreciated after elucidating the details of their kinetic mechanisms of action exploring the entire range of physiologically significant reactant concentrations. This book highlights the wide spectrum of allosteric enzyme modification in physiological occurrences as well as in pharmacological and biotechnological applications that embrace simple and multiple enzyme-modifier interactions. The reader is guided in the journey through this still partly uncharted territory with the aid of mechanistically-oriented criteria aimed at showing the logical way towards the identification of a particular mechanism.

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