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Lasso peptides form a growing family of fascinating ribosomally-synthesized and post-translationally modified peptides produced by bacteria. They contain 15 to 24 residues and share a unique interlocked topology that involves an N-terminal 7 to 9-residue macrolactam ring where the C-terminal tail is threaded and irreversibly trapped. The ring results from the condensation of the N-terminal amino group with a side-chain carboxylate of a glutamate at position 8 or 9, or an aspartate at position 7, 8 or 9. The trapping of the tail involves bulky amino acids located in the tail below and above the ring and/or disulfide bridges connecting the ring and the tail. Lasso peptides are subdivided into three subtypes depending on the absence (class II) or presence of one (class III) or two (class I) disulfide bridges. The lasso topology results in highly compact structures that give to lasso peptides an extraordinary stability towards both protease degradation and denaturing conditions. Lasso peptides are generally receptor antagonists, enzyme inhibitors and/or antibacterial or antiviral (anti-HIV) agents. The lasso scaffold and the associated biological activities shown by lasso peptides on different key targets make them promising molecules with high therapeutic potential. Their application in drug design has been exemplified by the development of an integrin antagonist based on a lasso peptide scaffold. The biosynthesis machinery of lasso peptides is therefore of high biotechnological interest, especially since such highly compact and stable structures have to date revealed inaccessible by peptide synthesis. Lasso peptides are produced from a linear precursor LasA, which undergoes a maturation process involving several steps, in particular cleavage of the leader peptide and cyclization. The post-translational modifications are ensured by a dedicated enzymatic machinery, which is composed of an ATP-dependent cysteine protease (LasB) and a lactam synthetase (LasC) that form an enzymatic complex called lasso synthetase. Microcin J25, produced by Escherichia coli AY25, is the archetype of lasso peptides and the most extensively studied. To date only around forty lasso peptides have been isolated, but genome mining approaches have revealed that they are widely distributed among Proteobacteria and Actinobacteria, particularly in Streptomyces, making available a rich resource of novel lasso peptides and enzyme machineries towards lasso topologies.
The American Peptide Society (APS) provides a forum for advancing and promoting knowledge of the chemistry and biology of peptides. The approximately one thousand members of the Society come from North America and from more than thirty other countries throughout the world. Establishment of the APS was a result of the rapid worldwide growth that has occurred in peptide-related research, and of the increasing interaction of peptide scientists with virtually all fields of science. Peptides for Youth: The Proceedings of the the 20th American Peptide Symposium will highlight many of the recent developments in peptide science, with a particular emphasis on how these advances are being applied to basic problems in biology and medicine. The 20th American Peptide Symposium will take place June 26 - 30, 2007 in Montreal, Canada.
Cyclic peptides are increasingly employed as chemical tools in biology and drug discovery. They have gained a lot of interest as alternative sources of new drugs to traditional small molecules. This book introduces cyclic peptides and provides a thorough overview of biosynthetic and fully synthetic approaches to their preparation. Following an introduction to cyclic peptides, biosynthetic and traditional chemical routes to cyclic peptides are reviewed. Due to their size, their synthesis is not trivial. Recent advances in the incorporation of novel structural units are presented in addition to how synthesis and biological methods can be combined. The chemical analysis of this molecular class is also discussed. Furthermore, chapters detail the progression of cyclic peptides as tools in biology and as potential drugs, providing a future vision of their importance. In total, this book provides the reader with a comprehensive view of the state-of-the-art of cyclic peptides, from construction to possible clinical utility. This book will be an essential resource for students, researchers and scientists within industry in medicinal, bioorganic, natural product and analytical chemistry fields.
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
Comprehensive Natural Products III, Third Edition, Seven Volume Set updates and complements the previous two editions, including recent advances in cofactor chemistry, structural diversity of natural products and secondary metabolites, enzymes and enzyme mechanisms and new bioinformatics tools. Natural products research is a dynamic discipline at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids and enzymes. This book reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine and to stimulate new ideas among the established natural products community. Provides readers with an in-depth review of current natural products research and a critical insight into the future direction of the field Bridges the gap in knowledge by covering developments in the field since the second edition published in 2010 Split into 7 sections on key topics to allow students, researchers and professionals to find relevant information quickly and easily Ensures that the knowledge within is easily understood by and applicable to a large audience
Antimicrobial Peptides, Volume 663 in the Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters on Unifying the classification of antimicrobial peptides in the Antimicrobial Peptide Database, Optimizing peptide library creation for PepSAVI-MS (RP libraries, etc.), Discovery of novel Antimicrobial peptides using BioProspecting, Screening for cysteine-stabilized scaffolds for developing protelytic-resistant AMPs, Exploring synergy and its role in antimicrobial peptide biology, Colorimetric assays for the rapid and high-throughput screening of antimicrobial peptide activity against diverse bacterial pathogens, and much more. Other chapters cover Liquid chromatography-mass spectrometry-based analysis of naturally occurring neuropeptide diastereomers, Multiplexed Quantitative Neuropeptidomics via DiLeu Isobaric Tagging, In vitro evaluation of antibiotic resistance via proteomics, Molecular networking-based strategies in mass spectrometry, Development of Macrocyclic antimicrobial peptides and peptoids, and a host of other timely topics. - Provides the authority and expertise of leading contributors from an international board of authors - Presents the latest release in Methods in Enzymology serials - Updated release includes the latest information on Antimicrobial Peptides
Prof Upton is the director of Amprologix, a company developing new bacteriocins; the other editors declare no competing interest in regard to editing this Research Topic.
The book will provide an overview of the advancement of fundamental knowledge and applications of antimicrobial peptides in biomedical, agricultural, veterinary, food, and cosmetic products. Antimicrobial peptides stand as potentially great alternatives to current antibiotics, and most research in this newly-created area has been published in journals and other periodicals. It is the editors’ opinion that it is timely to sum up the most important achievements in the field and provide the scientific community in a reference book. The goals of this project include illustrating the achievements made so far, debating the state of the art, and drawing new perspectives.
Poisonous mushrooms have fascinated scientists and laypersons alike for thousands of years. Almost all mushroom fatalities are due to the genus Amanita, whose poetic common names (death cap, destroying angel) attest to their lethality. In his classic 1986 book, Theodor Wieland covered the state of our knowledge about the chemistry and biochemistry of the toxins of Amanita mushrooms up until that time, with a particular focus on the decades of chemical research by him and the Wieland dynasty (including his father, brother, brother-in-law, and cousin). Wieland’s book is now mainly of historical interest, with its exhaustive overview of the early chemical studies done without benefit of methods taken for granted by modern chemists. This book is a complete top-to-bottom revision of Wieland’s 1986 book. The material covers history, chemistry, and biology with equal thoroughness. It should be of interest to natural products chemists and biologists, professional and amateur mycologists, and toxicologists. The three scientific fields that are most relevant to the book are natural products chemistry, mycology, and fungal molecular genetics. Dr. Walton is an expert in all three. To maximize the broad utility and appeal of the book, care has been taken to define all technical terms specific to a particular discipline, so that, for example, mycologists will be able to understand the relevant chemistry, and chemists will be able to understand the relevant fungal biology.
Handbook of Biologically Active Peptides, Second Edition, is the definitive, indispensable reference for peptide researchers, biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and endocrinologists. Its chapters are designed to be a source for workers in the field and enable researchers working in a specific area to examine related areas outside their expertise. Peptides play a crucial role in many physiological processes, including actions as neurotransmitters, hormones, and antibiotics. Research has shown their importance in such fields as neuroscience, immunology, pharmacology, and cell biology. The second edition of Handbook of Biologically Active Peptides presents this tremendous body of knowledge in the field of biologically active peptides in one single reference. The section editors and contributors represent some of the most sophisticated and distinguished scientists working in basic sciences and clinical medicine. - Presents all aspects of biologically active peptides in one resource - Features more than 20 sections spanning plant, bacterial, fungal, venom, and invertebrate peptides to general peptides - Includes immunological, inflammatory, cancer, vaccine, and neurotrophic peptides - Discusses peptide precursors, mRNA distribution, processing, and receptors, not just pathophysiological implications