Advances in Peptide and Peptidomimetic Design Inspiring Basic Science and Drug Discovery is a book dedicated to Prof. Victor J. Hruby on the occasion of his 80th birthday. This book includes twenty contributions from authors representing diverse multidisciplinary fields of scientific expertise, and is focused on the extraordinary potential of peptides and peptidomimetics as a surging therapeutic modality and as tools for basic research and technology development.
Peptide and Peptidomimetic Therapeutics: From Bench to Beside offers applied, evidence-based instruction on developing and applying peptide therapeutics in disease treatment, driving drug discovery, and improving patient care. Here, researchers, clinicians and students will find tools to harness the full power of peptides and peptidomimetics and improve bioavailability, stability, efficiency and selectivity of new therapeutics and their application in treatment plans. More than 20 leaders in the field share their approaches for identifying and advancing peptide and peptidomimetic therapeutics. Topics examined run from "bench to bedside," beginning with fundamental peptide science, protein-protein interactions and peptide synthesis. Later chapters examine modes for peptide drug delivery, including cell penetration peptide and peptidomimetic delivery, as well as the targeting of specific disease types, peptide therapeutics as applied to infectious disease, cancer, metabolic disorders, neurodegenerative disorders, and skin disorders, and antiparasitic and immunosuppressive peptidomimetics. - Helps researchers and clinicians harness the full of power of peptides and peptidomimetics in their daily work and drug discovery - Features chapters running from "bench to bedside, providing a thorough grounding in fundamental peptide science, drug delivery methods, and targeting of specific disease types - Features chapter contributions from international leaders in peptide science and drug development
This brief describes studies conducted by the authors on mid-size drugs utilizing peptides and peptidomimetics, and on the development of anti-HIV agents. Peptides are important biological molecules and have various physiological actions. Peptide-based drug discovery may help bring about the development of useful medicines that are highly safe and show potent pharmacological effects in small doses. Recently, it has been shown that there is an important drug-like space in the mid-sized region between low- and high-molecular-weight compounds. Thus, mid-size drugs such as peptide compounds are being focused on. To date, several peptidomimetics that mimic primary, secondary, and tertiary structures of peptides have been developed to maintain and improve biological activities and actions of peptides. In this book, the features and advantages of mid-size drugs are described in detail. In addition, the merits of utilizing peptidomimetics in the development of mid-size drugs are referred to. Understanding such peptide-derived mid-size drugs will lead to a comprehensive expansion of medicinal chemistry.
A peptidomimetic is a small protein-like chain designed to mimic a peptide with adjusted molecular properties such as enhanced stability or biological activity. It is a very powerful approach for the generation of small-molecule-based drugs as enzyme inhibitors or receptor ligands. Peptidomimetics in Organic and Medicinal Chemistry outlines the concepts and synthetic strategies underlying the building of bioactive compounds of a peptidomimetic nature. Topics covered include the chemistry of unnatural amino acids, peptide- and scaffold-based peptidomimetics, amino acid-side chain isosteres, backbone isosteres, dipeptide isosteres, beta-turn peptidomimetics, proline-mimetics as turn inducers, cyclic scaffolds, amino acid surrogates, and scaffolds for combinatorial chemistry of peptidomimetics. Case studies in the hit-to-lead process, such as the development of integrin ligands and thrombin inhibitors, illustrate the successful application of peptidomimetics in drug discovery.
With potentially high specificity and low toxicity, biologicals offer promising alternatives to small-molecule drugs. Peptide therapeutics have again become the focus of innovative drug development efforts backed up by a resurgence of venture funds and small biotechnology companies. What does it take to develop a peptide-based medicine? What are the key challenges and how are they overcome? What are emerging therapeutics for peptide modalities? This book answers these questions with a holistic story from molecules to medicine, combining the themes of design, synthesis and clinical applications of peptide-based therapeutics and biomarkers. Chapters are written and edited by leaders in the field from industry and academia and they cover the pharmacokinetics of peptide therapeutics, attributes necessary for commercially successful metabolic peptides, medicinal chemistry strategies for the design of peptidase-resistant peptide analogues, disease classes for which peptide therapeutic are most relevant, and regulatory issues and guidelines. The critical themes covered provide essential background information on what it takes to develop peptide-based medicine from a chemistry perspective and views on the future of peptide drugs. This book will be a valuable resource not only as a reference book for the researcher engaged in academic and pharmaceutical setting, from basic research to manufacturing and from organic chemistry to biotechnology, but also a valuable resource to graduate students to understand discovery and development process for peptide-based medicine.
Including case studies of macrocyclic marketed drugs and macrocycles in drug development, this book helps medicinal chemists deal with the synthetic and conceptual challenges of macrocycles in drug discovery efforts. Provides needed background to build a program in macrocycle drug discovery –design criteria, macrocycle profiles, applications, and limitations Features chapters contributed from leading international figures involved in macrocyclic drug discovery efforts Covers design criteria, typical profile of current macrocycles, applications, and limitations
Unique work on structure-based drug design, covering multiple aspects of drug discovery and development. Fully colored, many images, computer animations of 3D structures (these only in electronic form). Makes the spatial aspects of interacting molecules clear to the reader, covers multiple applications and methods in drug design. Structures by mode of action, no therapeutic areas. Of high relevance for academia and industrial research. Focus on gene technology in drug design, omics-technologies computational methods experimental techniques of structure determination multiple examples on mode of action of current drugs, ADME-tox properties in drug development, QSAR methods, combinatorial chemistry, biologicals, ribosome, targeting protein-protein interfaces.
Provides timely, comprehensive coverage of in vivo chemical reactions within live animals This handbook summarizes the interdisciplinary expertise of both chemists and biologists performing in vivo chemical reactions within live animals. By comparing and contrasting currently available chemical and biological techniques, it serves not just as a collection of the pioneering work done in animal-based studies, but also as a technical guide to help readers decide which tools are suitable and best for their experimental needs. The Handbook of In Vivo Chemistry in Mice: From Lab to Living System introduces readers to general information about live animal experiments and detection methods commonly used for these animal models. It focuses on chemistry-based techniques to develop selective in vivo targeting methodologies, as well as strategies for in vivo chemistry and drug release. Topics include: currently available mouse models; biocompatible fluorophores; radionuclides for radiodiagnosis/radiotherapy; live animal imaging techniques such as positron emission tomography (PET) imaging; magnetic resonance imaging (MRI); ultrasound imaging; hybrid imaging; biocompatible chemical reactions; ligand-directed nucleophilic substitution chemistry; biorthogonal prodrug release strategies; and various selective targeting strategies for live animals. -Completely covers current techniques of in vivo chemistry performed in live animals -Describes general information about commonly used live animal experiments and detection methods -Focuses on chemistry-based techniques to develop selective in vivo targeting methodologies, as well as strategies for in vivo chemistry and drug release -Places emphasis on material properties required for the development of appropriate compounds to be used for imaging and therapeutic purposes in preclinical applications Handbook of In Vivo Chemistry in Mice: From Lab to Living System will be of great interest to pharmaceutical chemists, life scientists, and organic chemists. It will also appeal to those working in the pharmaceutical and biotechnology industries.
Drug design is a complex, challenging and innovative research area. Structure-based molecular design has transformed the drug discovery approach in modern medicine. Traditionally, focus has been placed on computational, structural or synthetic methods only in isolation. This one-of-akind guide integrates all three skill sets for a complete picture of contemporary structure-based design. This practical approach provides the tools to develop a high-affinity ligand with drug-like properties for a given drug target for which a high-resolution structure exists. The authors use numerous examples of recently developed drugs to present "best practice" methods in structurebased drug design with both newcomers and practicing researchers in mind. By way of a carefully balanced mix of theoretical background and case studies from medicinal chemistry applications, readers will quickly and efficiently master the basic skills of successful drug design. This book is aimed at new and active medicinal chemists, biochemists, pharmacologists, natural product chemists and those working in drug discovery in the pharmaceutical industry. It is highly recommended as a desk reference to guide students in medicinal and chemical sciences as well as to aid researchers engaged in drug design today.
Protein-protein interactions (PPI) are at the heart of the majority of cellular processes, and are frequently dysregulated or usurped in disease. Given this central role, the inhibition of PPIs has been of significant interest as a means of treating a wide variety of diseases. However, there are inherent challenges in developing molecules capable of disrupting the relatively featureless and large interfacial areas involved. Despite this, there have been a number of successes in this field in recent years using both traditional drug discovery approaches and innovative, interdisciplinary strategies using novel chemical scaffolds. This book comprehensively covers the various aspects of PPI inhibition, encompassing small molecules, peptidomimetics, cyclic peptides, stapled peptides and macrocycles. Illustrated throughout with successful case studies, this book provides a holistic, cutting-edge view of the subject area and is ideal for chemical biologists and medicinal chemists interested in developing PPI inhibitors.
