Download or read book Synthesis of Peptide oligonucleotide Conjugates written by Maxim Antopolsky and published by . This book was released on 2002 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Synthesis and Characterisation of Peptide oligonucleotide Conjugates Derived from sheet Forming Or Collagen Mimetic Peptides written by Akiko Satō and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Simple and Double Conjugates of Peptides and Oligonucleotides written by Jordi Agramunt Pi and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "2,2-Disubstituted cyclopent-4-ene-1,3-diones (CPDs), which have been as non-hydrolysable maleimide analogs, have been found to possess an unexpected reactivity with N-terminal cysteines. Whilst maleimides react in an irreversible manner with all types of thiol nucleophiles, the Michael-type addition between CPDs and N-terminal cysteines, furnish a stable product with a mass 20 Da lower than the expected Michael-type adduct. This newly found reactivity can be applied for different purposes. In first instance, CPD-derivatized peptides can be used to synthesize conjugates by reaction with cystine-derivatized biomolecules such as peptides, peptide nucleic acids (PNAs) or oligonucleotides. In addition, the combination of the CPD-Cys reaction with other "click" reactions has been explored. In the first instance, the CPD-Cys reaction was paired the thia-Michael addition of thiols to maleimides using peptides containing two cysteines (one at the N-terminus). By first performing a CPD-Cys reaction at the N-terminus and then the addition of a maleimide, double conjugation could be easily achieved. In another case, combinations with oxime ligation and copper(I) catalyzed azide-alkyne (CuAAC) cycloadditions have been accomplished with a different degree of success. In the latter case, the CPD-Cys reaction has to be strictly performed before the CuAAC. In a further examination why this was the case, it was found out that CPDs react with azides to furnish two stable compounds one is the product of a 1,3-dipolar cycloaddition and the other results from nitrogen loss. Secondly, the bioconjugation of a splice-switching enhancing molecule known as "Retro-1" to an oligonucleotide with splice-switching activity described as 623 has been explored. In this part of the work, the complete synthesis of described Retro-1 has been accomplished in addition to that of other several analogues containing either a 1,3-diene, a thiol or a phosphoramidite group appending from two positions, nitrogen 4 or carbon 3. For this purpose, two synthetic strategies were followed one making use of valuable intermediates obtained from the Retro-1 synthesis and the other utilizing a properly protected lysine analogue to construct the Retro scaffold and introduce a reactive group at carbon 3. Additionally to all these reactants two oligonucleotides were synthesized: one with the 623 sequence and another with the same nucleobases but different order coined "scrambled". Both oligonucleotides were appended at the 5' position with a protected maleimide phosphoramidite (to obtain the corresponding maleimido-oligonucleotide and allow a Diels-Alder or thia-Michael addition to be performed) or the Retro-phosphoramidite. Finally, in this work the possibility of using 7-oxanorbornenes as dienophiles in the inverse electron-demanding Diels-Alder cycloaddition (IEDDA) with 3,6-disbustituted 1,2,4,5-tetrazines has been explored. The oxanorbornene moiety has been appended at the N-terminus and internal positions in peptides, and at the 5' and 3' positions of oligonucleotides utilizing solid-phase protocols. For the tetrazine counterpart optimization processes have been followed for the synthesis of N-terminal tetrazine peptides and for derivatization with biologically relevant molecules in reasonably good success. Once oxanorbornene- and tetrazine-containing derivatives were obtained it was observed that the IEDDA reaction took place satisfactorily, allowing for the synthesis of peptide and oligonucleotide conjugates with small molecules. In second term, the possibility of double conjugation involving at least one IEDDA reaction has been explored. The IEDDA has been combined with the Diels-Alder cycloaddition between a maleimide and a 1,3-diene, the thia-Michael between a thiol and a maleimide, the CPD-Cys reaction (utilizing CPDs and N-terminal cysteines as previously commented) and the aromatic nucleophilic substitution between a thiol and a chlorotetrazines. In every combination tested the double conjugate target compound was obtained, usually performing both reactions simultaneously, but sometimes in a "one-pot" fashion, with the sequential addition of reactants due to side reactions. In one case, it was necessary to isolate the intermediate monoconjugate because of difficulties related to undesired interferences between reactants." -- TDX.

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 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 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 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 Protocols for Oligonucleotide Conjugates written by Sudhir Agrawal and published by Humana Press. This book was released on 1993-11-30 with total page 377 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Design Synthesis and Assay of Paired ion Antisense Oligonucleotide peptide Conjugates written by Tianmin Zhu and published by . This book was released on 1995 with total page 354 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 Innovation and Perspectives in Solid Phase Synthesis written by Roger Epton and published by . This book was released on 1990 with total page 670 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work, based upon papers given at an international symposium, contains information on solid phase bio-organic synthesis. Descriptions of recent developments in the synthesis of specific biological macromolecules are given, along with data on artificial enzymes and more.

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 Nucleic Acids Chemistry written by Ramon Eritja and published by Walter de Gruyter GmbH & Co KG. This book was released on 2021-01-18 with total page 380 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book compiles recent research on the modification of nucleic acids. It covers backbone modifications and conjugation of lipids, peptides and proteins to oligonucleotides and their therapeutic use. Synthesis and application in biomedicine and nanotechnology of aptamers, fluorescent and xeno nucleic acids, DNA repair and artificial DNA are discussed as well.

Download or read book Peptide Nucleic Acids written by Peter E. Nielsen and published by Garland Science. This book was released on 2004 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: Peptide Nucleic Acids, Second Edition has been extensively revised, updated, and enlarged to contain many new chapters covering the most recent topics and applications in this fast-moving field. The book contains state-of-the-art protocols and applications on all aspects of peptide nucleic acids. Concepts are clearly explained with each chapter containing concise background information. Written by leading experts in the field, the book is an invaluable and complete reference work on this novel and exciting area.

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.