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Author: Isaac Abrrey Monreal Publisher: ISBN: Category : Drug delivery systems Languages : en Pages : 179
Book Description
The ability to access intracellular targets is of vital importance, especially as the number of druggable intracellular targets being identified increases greatly every year. Intracellular delivery poses a formidable barrier, as many potential therapeutics are impermeable to cell membranes hindering their practical application in medicinal development. Our research seeks to approach this problem using two unique peptide based approaches capable of improving on current peptide based intracellular delivery technologies. Our first approach is to functionalize oligomeric versions of an existing HIV-TAT peptide transduction domain capable of orthogonal cargo attachment. The second approach is the de novo generation of a new class of unnatural peptides based on a neuraminic acid scaffold amenable to traditional Fmoc based solid phase peptide synthesis with expected tunable secondary structures and enhanced biostability. Both approaches afford adaptability to expected potential problems and pose an exciting addition to the toolset for use in delivering cargos to increasingly important intracellular targets.
Author: Isaac Abrrey Monreal Publisher: ISBN: Category : Drug delivery systems Languages : en Pages : 179
Book Description
The ability to access intracellular targets is of vital importance, especially as the number of druggable intracellular targets being identified increases greatly every year. Intracellular delivery poses a formidable barrier, as many potential therapeutics are impermeable to cell membranes hindering their practical application in medicinal development. Our research seeks to approach this problem using two unique peptide based approaches capable of improving on current peptide based intracellular delivery technologies. Our first approach is to functionalize oligomeric versions of an existing HIV-TAT peptide transduction domain capable of orthogonal cargo attachment. The second approach is the de novo generation of a new class of unnatural peptides based on a neuraminic acid scaffold amenable to traditional Fmoc based solid phase peptide synthesis with expected tunable secondary structures and enhanced biostability. Both approaches afford adaptability to expected potential problems and pose an exciting addition to the toolset for use in delivering cargos to increasingly important intracellular targets.
Author: Aleš Prokop Publisher: Springer Science & Business Media ISBN: 9400712480 Category : Science Languages : en Pages : 871
Book Description
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.
Author: Diarmaid Murphy Publisher: LAP Lambert Academic Publishing ISBN: 9783838344188 Category : Languages : en Pages : 304
Book Description
The lipid bilayer, which comprises all cell membranes, represents a formidable barrier to the delivery of large hydrophilic molecules into cells. The ability to introduce information-rich molecules into cells is a challenge in the development of new therapeutics for diseases not currently amenable to small molecule intervention. This work focuses on the delivery of peptide-based molecules including; inhibitors, substrates and carriers into cells. A series of peptide-based inhibitors against caspase-3, an intracellular enzyme involved in apoptosis, were assessed for their cell membrane permeability. Proteolytic activation of a cell penetrating peptide was also investigated as a means of controlling the uptake of these carrier peptides into cells. Finally, the uptake and processing of an internally quenched Tat-caspase substrate was examined in cells undergoing apoptosis. This book may be of interest to scientists working in any area where large molecules need to be effectively delivered to cells. It may be of particular interest to those working on cell penetrating peptides, proteases or apoptosis.
Author: Publisher: ISBN: Category : Languages : en Pages : 24
Book Description
The use of peptides to mediate the delivery and uptake of nanoparticle (NP) materials by mammalian cells has grown significantly over the past 10 years. This area of research has important implications for the development of new therapeutic materials and for the emerging field of NP-mediated drug delivery. In this review, we highlight recent advances in the delivery of various NPs by some of the more commonly employed cellular delivery peptides and discuss important related factors such as NP-peptide bioconjugation, uptake efficiency, intracellular fate and toxicity. We also highlight various demonstrations of therapeutic applications of NP-peptide conjugates where appropriate. The paper concludes with a brief forward-looking perspective discussing what can be expected as this field develops in the coming years.
Author: Amaalia Emma Broad Publisher: ISBN: 9780494593059 Category : Languages : en Pages : 148
Book Description
The delivery of biomolecules by cell penetrating peptides (CPPs) is an innovative therapeutic strategy. However delivery efficiency is hindered by the entrapment of CPPs in vesicles, degradation, or recycling out of cells, which limits their delivery into the cell cytoplasm and nucleus. To overcome these barriers, we investigated a bacterial protein domain derived from Pseudomonas aeruginosa, Exotoxin A (ETA253-412) that is able to exit vesicular compartments. A series of CPP-ETA253-412 fusion proteins were constructed, expressed, and purified. Confocal microscopy and flow cytometry confirmed the internalization at 37°C of constructs containing CPPs (poly-arginine or TAT). In addition, constructs containing CPP-ETA253-412-eGFP were shown to relocate from endosomes to the cytosol. CPP-ETA253-412 constructs were also able to act as carriers of DNA cargos facilitating their delivery to the cytosol. The ETA253-412 translocation domain may prove useful for the intracellular delivery of drugs, protein therapeutics, siRNA delivery, and vaccine formulations.
Author: Heba Azmy Salim Publisher: ISBN: Category : Cyclic peptides Languages : en Pages : 0
Book Description
Biologics such as cyclic peptides, proteins, and nucleic acids are a class of therapeutics that have the ability to modulate diverse undruggable targets. Biologics can bind to flat and large surfaces involved in undruggable protein-protein interactions (PPIs) in comparable to small molecules. However, applications of biologics are restricted by their inefficient penetration to the cell membrane to reach their targets in the cytosol. Cell-penetrating peptides (CPPs) are short peptide sequences that can effectively deliver biologically active cargo into cells. This work is focused on utilizing cyclic CPPs as delivery tools for functional biologics including cyclic peptides and proteins targeting intracellular PPIs.
Author: Isaac Abrrey Monreal
Author: Isaac Abrrey Monreal
Author: Aleš Prokop
Author: Diarmaid Murphy
Author: Irene Martín Badajoz
Author: 
Author: Sharafudheen Pottanam Chali
Author: Ingo Potrykus
Author: Diarmaid Joseph Murphy
Author: Amaalia Emma Broad
Author: Heba Azmy Salim