Synthesis And Biophysical Characterization Of Cationic Amphipathic Ph Responsive Gene Delivery Peptides Containing Primary Beta Amine 2 3 Diaminopropionic Acid Residues And Secondary Beta Amine Mono Methylated Derivatives
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Synthesis And Biophysical Characterization Of Cationic Amphipathic Ph Responsive Gene Delivery Peptides Containing Primary Beta Amine 2 3 Diaminopropionic Acid Residues And Secondary Beta Amine Mono Methylated Derivatives
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Author : Jayneil Patel
language : en
Publisher:
Release Date : 2011
Synthesis And Biophysical Characterization Of Cationic Amphipathic Ph Responsive Gene Delivery Peptides Containing Primary Beta Amine 2 3 Diaminopropionic Acid Residues And Secondary Beta Amine Mono Methylated Derivatives written by Jayneil Patel and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with Gene therapy categories.
Delivery of therapeutic oligonucleotide sequences by cationic amphipathic histidine rich peptides like LAH4-L1 is modulated by peptide response to pH changes during endocytosis. pH sensitivity can be affected by the number of histidine residues, defining its transfection efficiency. Optimizing the gene delivery efficiencies of LAH4-L1 by increasing the number of histidine residues and therefore peptide charge is limited by the Coulombic interactions that stabilise a-helical self-associated peptide oligomers. Consequently, peptides containing six histidine residues function at a pH below that which occurs in the endosome, decreasing gene delivery capabilities. This limitation is expected to be overcome by substituting histidine residues with the more basic pH response 2,3- diaminopropionic acid (Dap). It is predicted that peptides containing 6 Dap residues will remain sensitive to pH changes observed in the endosome, leading to more efficient gene delivery peptide. To test these hypothesis peptides containing four and six Dap residues were synthesised. Analogously, derivatives containing mono-methylated P-amine Dap residues were formed in attempt to reduce cytotoxicity associated with primary amine peptides. Biophysical analysis was performed to determine the peptides pH response in key mechanisms that occur during gene delivery. It is shown that Dap residues can balance the Coulombic effects and respond at a more basic pH than histidine containing analogues. Whereas Dap substitution does not give increased gene delivery compared to LAH4-L1; mono-methylated Dap variants remain sensitive to pH changes in endocytosis and show increased gene delivery efficiencies compared to LAH4-L1. Peptides containing six mono-methylated Dap residues gave transfection results reproducible in serum greater than LAH4-L1 and comparable to commercially available peptide vectors.
Synthesis And Biophysical Characterisation Of Cationic Amphipathic Ph Responsive Gene Delivery Peptides Containing Primary Amine 2 3 Diaminopropionic Acid Residues And Secondary Amine Mono Methylated Derivatives
DOWNLOAD
Author : Jayneil Patel
language : en
Publisher:
Release Date : 2011
Synthesis And Biophysical Characterisation Of Cationic Amphipathic Ph Responsive Gene Delivery Peptides Containing Primary Amine 2 3 Diaminopropionic Acid Residues And Secondary Amine Mono Methylated Derivatives written by Jayneil Patel and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with Gene therapy categories.
Delivery of therapeutic oligonucleotide sequences by cationic amphipathic histidine rich peptides like LAH4-L1 is modulated by peptide response to pH changes during endocytosis. pH sensitivity can be affected by the number of histidine residues, defining its transfection efficiency. Optimizing the gene delivery efficiencies of LAH4-L1 by increasing the number of histidine residues and therefore peptide charge is limited by the Coulombic interactions that stabilise a-helical self-associated peptide oligomers. Consequently, peptides containing six histidine residues function at a pH below that which occurs in the endosome, decreasing gene delivery capabilities. This limitation is expected to be overcome by substituting histidine residues with the more basic pH response 2,3- diaminopropionic acid (Dap). It is predicted that peptides containing 6 Dap residues will remain sensitive to pH changes observed in the endosome, leading to more efficient gene delivery peptide. To test these hypothesis peptides containing four and six Dap residues were synthesised. Analogously, derivatives containing mono-methylated P-amine Dap residues were formed in attempt to reduce cytotoxicity associated with primary amine peptides. Biophysical analysis was performed to determine the peptides pH response in key mechanisms that occur during gene delivery. It is shown that Dap residues can balance the Coulombic effects and respond at a more basic pH than histidine containing analogues. Whereas Dap substitution does not give increased gene delivery compared to LAH4-L1; mono-methylated Dap variants remain sensitive to pH changes in endocytosis and show increased gene delivery efficiencies compared to LAH4-L1. Peptides containing six mono-methylated Dap residues gave transfection results reproducible in serum greater than LAH4-L1 and comparable to commercially available peptide vectors.
Telomerase Inhibition
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Author : Lucy Andrews
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-11-29
Telomerase Inhibition written by Lucy Andrews and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-11-29 with Medical categories.
This volume presents a compendium of the most recent and advanced methods applied to the rapidly expanding field of telomerase inhibition. The techniques described provide the researcher with a diverse and comprehensive set of tools for the study of telomerase inhibition. The volume is aimed at biochemists, molecular biologists, cancer researchers, and geneticists.
Targeted Drug Strategies For Cancer And Inflammation
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Author : Ann L. Jackman
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-05-05
Targeted Drug Strategies For Cancer And Inflammation written by Ann L. Jackman and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-05-05 with Medical categories.
Folate pathways are essential in metabolism and macromolecule synthesis. Antifolate drugs that are largely transported via a high capacity folate transporter (i.e. the reduced-folate carrier) and inhibit folate-dependent enzymes include the dihydrofolate reductase inhibitor, methotrexate, and the thymidylate synthase inhibitors, raltitrexed and pemetrexed. Major advances in folate research made within the last decade include (i) the approval of pemetrexed for the treatment of lung cancer and mesothelioma, and (ii) the demonstration that cell membrane-anchored folate receptors (FR) are exploitable for cancer and inflammatory disease management. FRs are not widely distributed in normal tissues, except on some luminal surfaces; however, they are accessible to systemically administered agents when expressed on many cancers as well as on activated macrophages involved in various inflammatory diseases. High affinity folate-radioisotope conjugates have been developed for imaging pathogenic FR-positive diseases, including cancer. Since the FR transports folates via a low capacity but high affinity endocytic pathway, a variety of FR-targeted antifolate drugs and folate conjugates bearing a wide range of payloads (including cytotoxic drugs) are currently being developed which exploit this property. The FR is also being utilized in immunotherapy approaches for the treatment of overexpressing cancers.
Nanotechnology For Nucleic Acid Delivery
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Author : Manfred Ogris
language : en
Publisher: Humana Press
Release Date : 2012-10-16
Nanotechnology For Nucleic Acid Delivery written by Manfred Ogris and has been published by Humana Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-10-16 with Science categories.
Nanotechnology and nucleic acid based therapies are two emerging fields in science whose combination has the potential to improve quality of life for patients suffering from various diseases that can so far only be treated in an unsatisfactory way. Nucleic acids offer the potential for highly selective treatment of such diseases or the highly specific modulation of gene expression with RNA interference. A key issue for successful nucleic acid therapies is the availability of a suitable delivery system. Here, the field of nanotechnology offers a multitude of possibilities to develop nanosized delivery vectors tailor-made for various local and systemic approaches. In Nanotechnology for Nucleic Acid Delivery: Methods and Protocols, experts in the field cover the area of nanoparticulate delivery of nucleic acids in terms of biosafety, particle synthesis as well as its application in cell culture. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Nanotechnology for Nucleic Acid Delivery: Methods and Protocols seeks to serve both professionals and novices with its well-honed methodologies.
Intracellular Delivery
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Author : Aleš Prokop
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-05-26
Intracellular Delivery written by Aleš Prokop and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-05-26 with Science categories.
This book features a special subsection of Nanomedicine, an application of nanotechnology to achieve breakthroughs in healthcare. It exploits the improved and often novel physical, chemical and biological properties of materials only existent at the nanometer scale. As a consequence of small scale, nanosystems in most cases are efficiently uptaken by cells and appear to act at the intracellular level. Nanotechnology has the potential to improve diagnosis, treatment and follow-up of diseases, and includes targeted drug delivery and regenerative medicine; it creates new tools and methods that impact significantly upon existing conservative practices. This volume is a collection of authoritative reviews. In the introductory section we define the field (intracellular delivery). Then, the fundamental routes of nanodelivery devices, cellular uptake, types of delivery devices, particularly in terms of localized cellular delivery, both for small drug molecules, macromolecular drugs and genes; at the academic and applied levels, are covered. The following section is dedicated to enhancing delivery via special targeting motifs followed by the introduction of different types of intracellular nanodelivery devices (e.g. a brief description of their chemistry) and ways of producing these different devices. Finally, we put special emphasis on particular disease states and on other biomedical applications, whilst diagnostic and sensing issues are also included. Intracellular delivery / therapy is a highly topical which will stir great interest. Intracellular delivery enables much more efficient drug delivery since the impact (on different organelles and sites) is intracellular as the drug is not supplied externally within the blood stream. There is great potential for targeted delivery with improved localized delivery and efficacy.
Dendritic Molecules
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Author : George R. Newkome
language : de
Publisher: John Wiley & Sons
Release Date : 2008-07-11
Dendritic Molecules written by George R. Newkome and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-07-11 with Science categories.
The first book on dendrimers! The authors, pioneers in this scientific field, describe basic principles and current developments in the rapidly evolving field of dendrimer research. All aspects of the subject are covered: the authors provide a historical overview, theoretical background, and discussions of the synthesis and applications of dendrimers. The book thus spans organic chemistry and more application-orientated disciplines like material science and pharmaceutical chemistry. The excellent, detailed list of references further increases the value of the book. The optimal presentation of the structural formulas of dendrimers - highly symmetrical giant molecules - helps the reader understand the sophisticated synthesis quickly. This book will set the standard for further monographs on this subject.
Handbook Of Cell Penetrating Peptides
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Author : Ulo Langel
language : en
Publisher: CRC Press
Release Date : 2006-08-15
Handbook Of Cell Penetrating Peptides written by Ulo Langel and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2006-08-15 with Medical categories.
Since the first Handbook of Cell-Penetrating Peptides was prepared in 2001, the wealth of new information on the use of these peptides as transport systems has in fact served to confound the field. The constant internal change in the field of cell-penetrating peptides (CPPs) is due to recent research uncovering apparent ambiguities in cellular upta
Monoclonal Antibodies And Their Functional Fragments In Research Diagnosis And Therapy
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Author : Menotti Ruvo
language : en
Publisher:
Release Date : 2022-02-11
Monoclonal Antibodies And Their Functional Fragments In Research Diagnosis And Therapy written by Menotti Ruvo and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2022-02-11 with categories.
Peptide Based Biomaterials
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Author : Mustafa O. Guler
language : en
Publisher: Royal Society of Chemistry
Release Date : 2020-11-18
Peptide Based Biomaterials written by Mustafa O. Guler and has been published by Royal Society of Chemistry this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-11-18 with Science categories.
Research and new tools in biomaterials development by using peptides are currently growing, as more functional and versatile building blocks are used to design a host of functional biomaterials via chemical modifications for health care applications. It is a field that is attracting researchers from across soft matter science, molecular engineering and biomaterials science. Covering the fundamental concepts of self-assembly, design and synthesis of peptides, this book will provide a solid introduction to the field for those interested in developing functional biomaterials by using peptide derivatives. The bioactive nature of the peptides and their physical properties are discussed in various applications in biomedicine. This book will help researchers and students working in biomaterials and biomedicine fields and help their understanding of modulating biological processes for disease diagnosis and treatments.