This book focuses on thielocin B1 (TB1), which was found to be an inhibitor of protein–protein interactions (PPIs) of proteasome assembling chaperone (PAC) 3 homodimer, and elucidates the mechanism by nuclear magnetic resonance (NMR) studies. Interfaces of PPIs recently have been expected to be novel therapeutic targets, while it is difficult to apply conventional methodology based on lock and key theory. The author achieved the first total synthesis of TB1 and its spin-labeled derivative to carry out NMR experiments because the supply of TB1 from natural sources was limited. Unique 2,2’,6,6’-tetrasubstituted diphenyl ether moiety of TB1 was synthesized from a depsidone skeleton by chemoselective reduction of lactone. In the process of elongating side wings, efficient formylation utilizing dichloromethyl methyl ether–silver trifluoromethanesulfonate was developed for the sterically hindered aromatic compound. NMR titration experiments and paramagnetic relaxation enhancement observation of PAC3 homodimer were performed with synthesized TB1 and its molecular probe, respectively. The results of the above NMR studies and additional in silico docking studies suggested that TB1 promotes the dissociation to monomeric PAC3 after interaction with PAC3 homodimer. The rare mechanism shown in this book indicates a potential novel drug target in the interfaces of PPIs with no cavity or groove.

Nature has evolved sequence-controlled polymers, such as DNA and proteins, over its long history. The recent progress of synthetic chemistry, DNA recombinant technology, and computational science, as well as the elucidation of molecular mechanisms in biological processes, drive us to design ingenious polymers that are inspired by naturally occurring polymers, but surpass them in specialized functions. The term “designer biopolymers” refers to polymers which consist of biological building units, such as nucleotides, amino acids, and monosaccharides, in a sequence-controlled manner. This book particularly focuses on the self-assembling aspect of designer biopolymers. Self-assembly is one common feature in biopolymers that is used to realize their dynamic biological activities and is strictly controlled by the sequence of biopolymers. In a broad sense, the self-assembly of biopolymers includes a double-helix formation of DNA, protein folding, and higher-order protein assembly (e.g., viral capsids). Designer biopolymers are now going beyond what nature evolved: researchers have generated DNA origami, protein cages, peptide nanofibers, and gels. This book illustrates the latest interdisciplinary work on self-assembling designer biopolymers. As shown by this book, the self-assembly of biopolymers has a great impact on a variety of research fields, including molecular biology, neurodegenerative diseases, drug delivery, gene therapy, regenerative medicine, and biomineralization. Designer biopolymers will help researchers to better understand biological processes, as well as to create innovative molecular systems. We believe that this book will provide readers with new ideas for their molecular design strategies for frontier research.

Ionic and Organometallic-Catalyzed Organosilane Reductions provides an up-to-date, comprehensive review of reductions with organosilanes. Both ionic and catalyst-mediated reaction types are included, with appropriate reference to reaction mechanisms where they have been elucidated. The text also provides a wide variety of organic functional group reductions by organosilicon hydrides, and includes a substantial discussion of asymmetric reductions. All known examples have been compiled in thirty-four easily scanned, comprehensive tables compiled from 809 original articles. This is a must-have reference book for all synthetic organic chemists working in academic and industrial laboratories.

Provides comprehensive information on the most useful protective groups for the hydroxyl, amino, carboxyl, carbonyl, and sulfhydryl groups. Discusses the chemistry of the classes of protective groups, as well as that of the individual protective groups within the class using structures, equations and references. Reactivity Charts for each class of protective group serve as an aid in their appropriate choice and provide estimates of their relative reactivities toward 108 prototype reagents.

This book differs from others on name reactions in organic chemistry by focusing on their mechanisms. It covers over 300 classical as well as contemporary name reactions. Biographical sketches for the chemists who discovered or developed those name reactions have been included. Each reaction is delineated by its detailed step-by-step, electron-pushing mechanism, supplemented with the original and the latest references, especially review articles. This book contains major improvements over the previous edition and the subject index is significantly expanded.

This book differs from others on name reactions in organic chemistry by focusing on their mechanisms. It covers over 300 classical as well as contemporary name reactions. Biographical sketches for the chemists who discovered or developed those name reactions have been included. Each reaction is delineated by its detailed step-by-step, electron-pushing mechanism, supplemented with the original and the latest references, especially review articles. This book contains major improvements over the previous edition and the subject index is significantly expanded.

"This compendium includes almost all presently known species of ascomycetes that have been reported in soil and which sporulate in culture. They constitute a very broad spectrum of genera belonging to very diverse orders, but mainly to the Onygenales, Sordariales, Eurotiales, Thelebolales, Pezizales, Melanosporales, Pleosporales, Xylariales, Coniochaetales and Microascales. The goal of this book is to provide sufficient data for users to recognise and identify these species. It includes the description of 146 genera and 698 species. For each genus a dichotomous key to facilitate species identification is provided and for each genus and species the salient morphological features are described. These descriptions are accompanied by line drawings illustrating the most representative structures. Light micrographs, supplemented by scanning electron micrographs and Nomarski interference contrast micrographs of most of the species treated in the book are also included. In addition, numerous species not found in soil but related to those included in this book are referenced or described. This book will be of value not only to soil microbiologists and plant pathologists concerned with the soilborne fungi and diseases, but also to anyone interested in identifying fungi in general, because many of the genera included here are not confined to soil. Since most of the fungi of biotechnological or clinical interest (dermatophytes, dimorphic fungi and opportunists) are soil-borne ascomycetes, the content of this book is of interest for a wide range of scientists."--pub. desc.

Michael D. Wendt Protein-Protein Interactions as Drug Targets Shaomeng Wang , Yujun Zhao , Denzil Bernard , Angelo Aguilar , Sanjeev Kumar Targeting the MDM2-p53 Protein-Protein Interaction for New Cancer Therapeutics Kurt Deshayes , Jeremy Murray , Domagoj Vucic The Development of Small-Molecule IAP Antagonists for the Treatment of Cancer John F. Kadow , David R. Langley , Nicholas A. Meanwell , Michael A. Walker , Kap-Sun Yeung , Richard Pracitto Protein-Protein Interaction Targets to Inhibit HIV-1 Infection Nicholas A. Meanwell , David R. Langley Inhibitors of Protein-Protein Interactions in Paramyxovirus Fusion – a Focus on Respiratory Syncytial Virus Andrew B. Mahon , Stephen E. Miller , Stephen T. Joy , Paramjit S. Arora Rational Design Strategies for Developing Synthetic Inhibitors of Helical Protein Interfaces Michael D. Wendt The Discovery of Navitoclax, a Bcl-2 Family Inhibitor

Sendai virus (SeV) is not just a mouse pathogen but is evolving into a cutting-edge component of biotechnology. SeV reverse genetics originating from a pure academic need to settle long-held questions in the biology and pathogenicity of nonsegmented negative strand RNA viruses (Mononegavirales) is about to bear the impressive fruit of multipurpose cytoplasmic (non-integrating) RNA vectors. This book brings together in one source the SeV biology revealed by conventional approaches and reverse genetics, the methods to construct the first-generation SeV vector and to generate safer versions, and the applications in medical settings that have left or are about to leave the laboratory bench. The applications, which already are diverse and have high medical impact, include use as vaccine vectors against AIDS and respiratory virus infections, creation of BioKnife to resect malignant tumors, induction of “footprint (transgene) free” pluripotent stem cells, and gene therapy for peripheral arterial disease. These achievements—which are just a few of many examples—were attainable only after rigorously incorporating the rich knowledge of SeV biology that has accumulated during the several decades since the discovery of the virus. Application of SeV vector is certain to expand greatly because of its extremely high performance in transgene expression and its remarkable target cell breadth.