Download or read book Development of a Novel Methodology for the Synthesis of Oligonucleotide peptide Conjugates written by Simone Zaramella and published by . This book was released on 2004 with total page 60 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Oligonucleotide Synthesis written by Piet Herdewijn and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 436 pages. Available in PDF, EPUB and Kindle. Book excerpt: A collection of powerful new techniques for oligonucleotide synthesis and for the use of modified oligonucleotides in biotechnology. Among the protocol highlights are a novel two-step process that yields a high purity, less costly, DNA, the synthesis of phosphorothioates using new sulfur transfer agents, the synthesis of LNA, peptide conjugation methods to improve cellular delivery and cell-specific targeting, and triple helix formation. The applications include using molecular beacons to monitor the PCR amplification process, nuclease footprinting to study the sequence-selective binding of small molecules of DNA, nucleic acid libraries, and the use of small interference RNA (siRNA) as an inhibitor of gene expression.
Download or read book Novel Methodology for the Linking of Oligonucleotide peptide Conjugates written by Jason Robert Epstein and published by . This book was released on 1999 with total page 136 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Novel Approaches to Oligonucleotide Conjugation to a Cell Penetrating Tat Peptide written by Victoria Steven and published by . This book was released on 2009 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Modifed oligonucleotides are routinely employed as bioanalytical probes for use in diagnostics; however, a major limiting factor in oligonucleotide-based diagnostics is poor cellular uptake. This can be overcome by covalent attachment of a cell penetrating peptide. Diels-Alder cycloaddition is an attractive methodology for oligonucleotide peptide conjugation; the reaction is fast and chemoselective and the reaction rate is greatly enhanced in aqueous media. An oligonucleotide sequence has been derivatised with a series of dienes at the 5'- terminus, through chemical synthesis of a series of unique dienyl modified phosphoramidites. Investigation into the effect of diene type on the efficiency of conjugation to a maleimido derivatised Tat peptide derivative, via the Diels-Alder cycloaddition, has been performed. The optimal diene for biomolecule conjugation was found to be cyclohexadiene in the conjugation of oligonucleotides to a cell penetrating peptide via Diels-Alder cycloaddition for the first time. An oligonucleotide sequence has also been derivatised with cyclohexadiene internally; Diels-Alder cycloadditions of these oligonucleotides to a maleimido derivatised Tat peptide derivative were also successful. However, oligonucleotide conjugation to Tat peptide via Diels-Alder cycloaddition of fluorescently labelled oligonucleotides for visualisation in cell studies has not been as successful as for unlabelled oligonucleotides. Generation of a biocatalytic DNA sequence for the acceleration of Diels-Alder cycloadditions has been attempted. Through a SELEX-type process, a DNA sequence has been isolated for experimental determination of its potential as a biological catalyst for Diels-Alder cycloadditions. Oligonucleotide conjugation to Tat peptide via gold nanoparticles has been achieved. Chemical synthesis of a dithiolated, long-chain PEGylated ligand allowed covalent attachment of Tat peptide to gold nanoparticles. Bifunctionalisation of gold nanoparticles with oligonucleotides and this ligand, followed by covalent attachment of Tat peptide generated the desired conjugate. The conjugates have been shown to hybridise successfully with the complementary oligonucleotide sequence, thereby displaying potential for their use as bioanalytical probes. Methods for quantification of both oligonucleotides and Tat peptide conjugated to gold nanoparticles, by enzyme hydrolysis, have been developed.
Download or read book Peptide Nucleic Acids written by Peter E. Nielsen and published by Springer Science & Business Media. This book was released on 2008-02-04 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Peptide nucleic acids (PNAs) have now existed for slightly more than ten years, with the interest in and applications of this pseudopeptide DNA mimic steadily increasing during the entire period. PNAs have rapidly attracted the attention of scientists from a diversity of fields ranging from (bio)organic and biophysical chemistry to prebiotic evolution, and from molecular biology to genetic diagnostics and drug development. Many of the applications take advantage of the unique properties of PNA—an uncharged pseudopeptide—that distinguish this DNA mimic from more traditional DNA analogs. Rather than trying to create a comprehensive collection of all published methods and protocols involving PNA—many of which have not yet been validated— I have decided to concentrate on select protocols that are either very well established by several groups around the world, such as PCR-clamping and in situ hybridization, or on new methods that may have broader future impact. Basic methods for PNA oligomer synthesis and analyses have also been included. I am very grateful to those friends and colleagues who have enthusiastically contributed their work, discussions, and writing, and thereby made this book possible. Peter E. Nielsen v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix IINTRODUCTION 1 PNA Technology Peter E. Nielsen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 II CHEMISTRY 2 Solid Phase Synthesis of PNA Oligomers Frederik Beck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3 Synthesis of PNA-Peptide Conjugates Satish Kumar Awasthi and Peter E. Nielsen. . . . . . . . . . . . . . . . . . 43 4 Parallel Synthesis of PNA-Peptide Conjugate Libraries Satish Kumar Awasthi and Peter E. Nielsen. . . . . . . . . . . . . . . . . .
Download or read book Synthesis of Therapeutic Oligonucleotides written by Satoshi Obika and published by Springer. This book was released on 2018-12-08 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the latest knowledge on a broad range of topics relating to the synthesis of natural and artificial oligonucleotides with therapeutic potential. Nucleic acid-based therapeutics are attracting much attention, and numerous therapeutic oligonucleotides, such as antisense oligonucleotides, siRNAs, splice-switching oligonucleotides, and nucleic acid aptamers, are being evaluated in clinical trials for the treatment of a variety of diseases. Synthesis of Therapeutic Oligonucleotides covers a broad range of topics in the field that are of high relevance to researchers, including the synthesis of natural and chemically modified oligonucleotides, the development of novel nucleic acid analogs, industrial scale synthesis and purification of oligonucleotides, and important aspects of chemistry, manufacturing, and controls (CMC). The aim is to provide new insights and inspire fresh ideas in nucleic acid chemistry that may ultimately lead to novel concepts and techniques and the discovery of more effective nucleic acid drugs. The book will be of high value for both established researchers in the field and students intending to specialize in nucleic acid chemistry research.
Download or read book Oligonucleotide Synthesis written by Piet Herdewijn and published by Humana. This book was released on 2004-09-01 with total page 436 pages. Available in PDF, EPUB and Kindle. Book excerpt: A collection of powerful new techniques for oligonucleotide synthesis and for the use of modified oligonucleotides in biotechnology. Among the protocol highlights are a novel two-step process that yields a high purity, less costly, DNA, the synthesis of phosphorothioates using new sulfur transfer agents, the synthesis of LNA, peptide conjugation methods to improve cellular delivery and cell-specific targeting, and triple helix formation. The applications include using molecular beacons to monitor the PCR amplification process, nuclease footprinting to study the sequence-selective binding of small molecules of DNA, nucleic acid libraries, and the use of small interference RNA (siRNA) as an inhibitor of gene expression.
Download or read book The Synthesis of Oligonucleotide Peptide Conjugates Using Diels Alder Chemistry written by Leann Tait and published by . This book was released on 2006 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Therapeutic Oligonucleotides written by Jens Kurreck and published by Royal Society of Chemistry. This book was released on 2008 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compelling overall update on current status of RNA interference
Download or read book Protocols for Oligonucleotides and Analogs written by Sudhir Agrawal and published by Springer Science & Business Media. This book was released on 1993-08-31 with total page 503 pages. Available in PDF, EPUB and Kindle. Book excerpt: When first conceived, not only was the aim of Protocols for Oligo nucleotides and Analogs to provide wide coverage of the ohgonuc- otide chemistry field for readers who are well versed within the field, but also to give investigators just entering into the field a new perspective. The very first book on this topic was edited and published by Michael Gait in 1984, in whose laboratory I encountered the newer aspects of oligonucleotide chemistry. Since then, oligonucleotide research has developed to such an extent that its uses extend far beyond basic studies, and now find wide application throughout clinical science as well. Until recently, the major application of oligonucleotides has been in the area of DNA-based diagnostic and "antisense oligonucleotid- based therapeutic approaches. However, oligonucleotides are now also being used as therapeutic agents and are thus frequently found in clinical trials in humans. Synthesis of unmodified oligonucleotides using automated synthe sizers has become a common practice in numerous laboratories. How ever, improvements on the existing techniques and the introduction of ever newer methods for oligonucleotide synthesis is constantly driving ahead in the leading research laboratories. And several new oligonucle otide analogs have been synthesized and studied for their individual prop erties in recent years. The present volume strives to bring the readers the most up-to-date information on the newest aspects of synthesis of oligo nucleotides and their analogs. A separate volume covers synthesis of oligonucleotide conjugates, along with most of the analytical techniques presently used for analysis of oligonucleotides.
Download or read book Peptide Synthesis and Applications written by John Howl and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 263 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Peptide Conjugation to Enhance Oligonucleotide Delivery written by Justin Mahoney Wolfe and published by . This book was released on 2018 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: The intracellular delivery of functional macromolecules remains an outstanding challenge in biomedicine. While small molecules can diffuse through the plasma membrane, many large therapeutic molecules are not internalized to an appreciable extent. One strategy to improve cell uptake involves linking the molecule of interest to a cell-penetrating peptide (CPP). CPPs are widely employed to enhance macromolecule delivery, with hundreds of different peptides and modifications reported to improve cellular uptake. In this thesis, CPPs were systematically investigated and chemically altered to facilitate the delivery of antisense oligonucleotides. To accurately compare the existing CPPs, 64 CPP sequences were synthesized, conjugated to oligonucleotides, and assayed for delivery. These CPPs showed a range of effectiveness, with some CPPs hindering the delivery of oligonucleotide cargo and others leading to a 10-fold increase in oligonucleotide activity. To help identify which CPPs might be valuable for oligonucleotide delivery specifically, a computational model was developed to predict, de novo, whether or not a CPP will be effective. When experimentally validated, this model successfully predicted which sequences would improve oligonucleotide delivery greater than 3-fold. Multiple strategies were employed to improve CPP effectiveness. First, arginine-rich CPPs were chemically modified with perfluoroarenes. Cyclic and bicyclic CPPs were synthesized by linking multiple cysteine residues together with a perfluoroarene. After oligonucleotide conjugation, these peptides led to a 14-fold increase in delivery. Second, two different CPPs were combined into one long chimeric sequence. The CPP chimeras were highly active, leading to a 20-fold increase in oligonucleotide delivery. Third, the idea of combining multiple CPPs led to the development of a method for the rapid synthesis combinatorial peptide conjugates. Using the judicious choice of bioconjugation chemistry, highly-active modular constructs were synthesized that contain three peptides linked to one oligonucleotide. In addition to CPPs for oligonucleotide delivery, one section of this thesis employed perfluoroaryl macrocyclic peptides to address the challenge of peptide delivery across the blood-brain barrier. An additional section developed a new peptide conjugation strategy that uses palladium-peptide oxidative addition complexes as solid, storable, and water-soluble reagents for bioconjugation.
Download or read book The Development of Novel Methods for the Synthesis of Histidine containing Peptides written by John David Richards and published by . This book was released on 1981 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Development of Methodology for the Chemical Synthesis of Oligonucleotides written by Murray Alexander Bremner and published by . This book was released on 1997 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Peptide Synthesis written by Waleed M. Hussein and published by Humana. This book was released on 2019-12-27 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a variety of procedures for synthetically producing peptides and their derivatives, ensuring the kind of precision that is of paramount importance for successful synthesis. Numerous techniques relevant to drugs and vaccines are explored, such as conjugation and condensation methodologies. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Peptide Synthesis: Methods and Protocols serves as an essential guide to the many crucial processes that will allow researchers to efficiently prepare, purify, characterize, and use peptides for chemical, biochemical, and biological studies.
Download or read book Efficient Methods for Oligonucleotide Conjugation and Novel Hybridization Probes Using Photolabile Orthogonal Solid Phase Synthesis Supports written by Dustin Lee McMinn and published by . This book was released on 1998 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Methodology for the Synthesis of Intercalator Peptide Conjugates written by Jeffrey Peter Mitchell and published by . This book was released on 2004 with total page 364 pages. Available in PDF, EPUB and Kindle. Book excerpt:
