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(cont.) Biopanning a random peptide YSD library and subsequent characterization of the identified binding partners revealed the importance of multiple basic amino acids in the binding event. Study of rationally designed basic peptides revealed a preference for those amino acids to be spaced in such a manner that maximized simultaneous interaction with the surface. Fusing peptides to maltose binding protein (MBP) allowed for quantitative affinity measurement with the best peptides having low nanomolar equilibrium dissociation constants. Finally, peptides were demonstrated as facile affinity tags for protein immobilization in micro-patterning and biosensor assays.
Rational design and analysis of protein databanks via data-driven algorithms have significantly accelerated drug discovery, in particular, and a wide range of biological research topics, in general, during last decades. A similar approach is gaining momentum in materials research but has garnered limited attention in areas such as the design of soft interfaces formed by solid-binding peptides at solid materials interfaces. The GEMSEC Laboratory (Genetically-Engineered Materials Science and Engineering Center) has been working towards expanding this strategy in materials research via the development of peptide-based bioelectronic interfaces incorporating solid-binding peptides and single layer materials and, thereby, bridge biology to solid-state devices such as graphene field-effect transistors. We are presented with a challenge in peptide-based materials design as, in general, a vast store of relevant data is not available in materials science that is similar to protein databanks that are available in fields such as molecular biology. Thus, there is need for a knowledge-base, but that requires decades of research to draw on. In the present research, this was accounted by utilizing an innovative integration of combinatorial selection of solid-binding peptides, their rational design and bioinformatics based approach to model specific peptide-material interactions. From a data-base of 10s if not hundreds of peptides selected by this approach, the basis of the present method is to generate libraries of materials specific super-peptides that can attach, assemble and perform specific functions on atomically-flat material surfaces. As solid-state systems, single atomic layer materials, such as graphene and those that provide flat surfaces, such as quartz, have been chosen. Using these libraries, peptides that are capable of binding to their counterpart solid material of interest can be identified by performing combinatorial selection based on phage display approach. Typically, 50+ individual peptides are selected from of an original pool of ~1015 variants, which are then classified based on their binding strength using, e.g., fluorescent microscopy. Needleman-Wunsch based similarity analysis and machine learning algorithms are then used to create a scoring matrix capable of identifying robust and weak binders for the particular material amongst millions of random permutations of amino acid sequences in the peptides. The most powerful of these binders are fed into a decision-tree based rational design consisting of selection rules on hydropathicity, iconicity, aromaticity, and polarity of peptides identified to be capable of self-assembly from the previously conduted experiments. This process filters peptides and identifies those that are capable of strongly binding to as well as readily assembling on the atomically flat solid crystals. These model-based designed peptide sequences are then chemically synthesized and subsequently evaluated experimentally in terms of their binding and assembly characteristics using, e.g., atomic force microscopy to validate the success of the predictive model. As the experimental data become available in the assembly of the peptides under specific experimental parameters that are related to the particular chemistry of the sequences, the approach progressively creates a better outcome. Consequently, the model upon each experimental validation is further improvised and provides further knowledge and supply related sequences to the library to advance peptide-guided functional solid-state materials for practical nanotechnology and nanomedicine applications.
Hands-on experts describe in step-by-step detail the key methodologies of contemporary peptide synthesis and illustrate their numerous applications. The techniques presented include protocols for chemical ligation, the synthesis of cyclic and phosphotyrosine-containing peptides, lipoamino acid- and sugar-conjugated peptides, and peptide purification and analyses. Additional chapters detail methodologies and instrumentation for high-throughput peptide synthesis, many different applications of peptides as novel research tools and biological probes, and the design and application of fluorescent substrate-based peptides that can be used to determine the selectivity and activity of peptidases. A practical guide to the identification of proteins using mass spectrometric analyses of peptide mixtures is also included.
Synthesis of Polypeptides by Ring-Opening Polymerization of α-Amino Acid N-Carboxyanhydrides, by Jianjun Cheng and Timothy J. Deming.- Peptide Synthesis and Self-Assembly, by S. Maude, L. R. Tai, R. P. W. Davies, B. Liu, S. A. Harris, P. J. Kocienski and A. Aggeli.- Elastomeric Polypeptides, by Mark B. van Eldijk, Christopher L. McGann, Kristi L. Kiick andJan C. M. van Hest.- Self-Assembled Polypeptide and Polypeptide Hybrid Vesicles: From Synthesis to Application, by Uh-Joo Choe, Victor Z. Sun, James-Kevin Y. Tan and Daniel T. Kamei.- Peptide-Based and Polypeptide-Based Hydrogels for Drug Delivery and Tissue Engineering, by Aysegul Altunbas and Darrin J. Pochan.-
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.
Bioconjugate Techniques, 2nd Edition, is the essential guide to the modification and cross linking of biomolecules for use in research, diagnostics, and therapeutics. It provides highly detailed information on the chemistry, reagent systems, and practical applications for creating labeled or conjugate molecules. It also describes dozens of reactions with details on hundreds of commercially available reagents and the use of these reagents for modifying or cross linking peptides and proteins, sugars and polysaccharides, nucleic acids and oligonucleotides, lipids, and synthetic polymers. A one-stop source for proven methods and protocols for synthesizing bioconjugates in the lab Step-by-step presentation makes the book an ideal source for researchers who are less familiar with the synthesis of bioconjugates More than 600 figures that visually describe the complex reactions associated with the synthesis of bioconjugates Includes entirely new chapters on the latest areas in the field of bioconjugation as follows: Microparticles and nanoparticlesSilane coupling agentsDendrimers and dendronsChemoselective ligationQuantum dotsLanthanide chelatesCyanine dyesDiscrete PEG compoundsBuckyballs,fullerenes, and carbon nanotubesMass tags and isotope tagsBioconjugation in the study of protein interactions
Introduces readers to the field of inorganic materials, while emphasizing synthesis and modification techniques Written from the chemist's point of view, this newly updated and completely revised fourth edition of Synthesis of Inorganic Materials provides a thorough and pedagogical introduction to the exciting and fast developing field of inorganic materials and features all of the latest developments. New to this edition is a chapter on self-assembly and self-organization, as well as all-new content on: demixing of glasses, non-classical crystallization, precursor chemistry, citrate-gel and Pechini liquid mix methods, ice-templating, and materials with hierarchical porosity. Synthesis of Inorganic Materials, 4th Edition features chapters covering: solid-state reactions; formation of solids from the gas phase; formation of solids from solutions and melts; preparation and modification of inorganic polymers; self-assembly and self-organization; templated materials; and nanostructured materials. There is also an extensive glossary to help bridge the gap between chemistry, solid state physics and materials science. In addition, a selection of books and review articles is provided at the end of each chapter as a starting point for more in-depth reading. -Gives the students a thorough overview of the fundamentals and the wide variety of different inorganic materials with applications in research as well as in industry -Every chapter is updated with new content -Includes a completely new chapter covering self-assembly and self-organization -Written by well-known and experienced authors who follow an intuitive and pedagogical approach Synthesis of Inorganic Materials, 4th Edition is a valuable resource for advanced undergraduate students as well as masters and graduate students of inorganic chemistry and materials science.
Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.
Non-covalent interactions, which are the heart of supramolecular chemistry are also the basis of most important functions of living systems. The ability to apply supramolecular chemistry principles to the life sciences, such as designing synthetic host compounds to selectively interact within biological targets, has gained wide appeal due the vast number of potential applications. Supramolecular Systems for Biomedical Fields provides in sixteen chapters a comprehensive overview of these applications. Each chapter covers a specific topic and is written by internationally renowned experts in that area. Sensing of bioactive inorganic ions and organic substrates is the focus of several contributions, as well as interactions with proteins and nucleic acids. Specific chapters are devoted to cyclodextrins, calixarenes and cucurbiturils as most frequently used receptors, including applications such as drug delivery and protection, gene transfer and others. Other chapters address the use of combinatorial libraries, molecular imprinting techniques, enzyme assays, supramolecular gels, bioimaging, drug activation, photodynamic therapy, and antitumour metal complexes. This timely publication will appeal to graduate students and researchers from chemical, pharmaceutical, biological, and medicinal fields interested in the supramolecular chemistry of biological systems and their practical potentials.