One of the major problems with drug delivery is the inability of large hydrophilic compounds to pass through the lipid membrane of the cell, thus making drugs such as polypeptides and oligonucleotides of limited therapeutic value.
Author: Ulo Langel
Publisher: CRC Press
One of the major problems with drug delivery is the inability of large hydrophilic compounds to pass through the lipid membrane of the cell, thus making drugs such as polypeptides and oligonucleotides of limited therapeutic value. Until recently, the transport of such molecules into the cytoplasmic and nuclear compartments of living cells seemed a
In this book, a summary and update of the most important areas of CPP research are presented, whilst raising relevant questions for further development. The CPP sequences are presented and discussed throughout the book.
Author: Ülo Langel
In this book, a summary and update of the most important areas of CPP research are presented, whilst raising relevant questions for further development. The CPP sequences are presented and discussed throughout the book. The methods for testing CPP mechanisms are discussed in detail. Various approaches for the testing of endocytotic pathways of CPP uptake are also described. Different CPP uptake experiments are compared since it is becoming clear that it is often best to apply several methods in a complementary manner in order to most comprehensively evaluate CPP uptake mechanisms due to the complexity of these processes. A brief summary of functionality issues of CPPs, both in vitro and in vivo are discussed. Therapeutic potential of CPPs and commercial developments are discussed. The monograph is written for researchers and students in the field.
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.
Author: Ulo Langel
Publisher: CRC Press
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
Divided into three parts this volume summarizes the most important areas of Cell-Penetrating Peptides (CPP) research .
Author: Ülo Langel
Publisher: Humana Press
Divided into three parts this volume summarizes the most important areas of Cell-Penetrating Peptides (CPP) research . Part one briefly presents the historical background of CPP studies and the classifications of the available CPPs, and then summarizes the approaches for prediction of novel CPPs. Part two mainly describes the methods for studies of “naked” CPPs, that is, CPPs without conjugated cargos. Last but not least part three presents a representative and brief summary of functionality issues of CPPs, both in vitro and in vivo. As a volume in the highly successful Methods in Molecular Biology series, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Cell-Penetrating Peptides: Methods and Protocols, Second Edition hopes to raise relevant questions for further development.
Cell penetrating peptides (CPPs) are short 8-30 amino acid polypeptides that are able to transit across the semi-permeable plasma membrane of living cells, and deliver bound cargoes to the cytoplasm and other subcellular locations (e.g. ...
Author: Jordan Tan Pepper
Cell penetrating peptides (CPPs) are short 8-30 amino acid polypeptides that are able to transit across the semi-permeable plasma membrane of living cells, and deliver bound cargoes to the cytoplasm and other subcellular locations (e.g. nucleus, plastid organelles etc). The use of CPPs in plant cells and tissues remains a small and little researched field compared with the greater body of animal based research imperatives. The present research describes firstly, the measured interaction of the chosen model CPP Tat¬2 with the cell wall of microspores (i.e. microspore exine), secondly the reduction of the size and increase in regularity (measured as polydispersity) of Tat2 nucleic acid polyplexes and the unique empirical derivation of pseudo-kinetic parameters of nucleic acid CPP aggregation. Additionally several attempts to apply the findings from this research in plant cells and tissues are presented and discussed throughout.
Abstract: Short interfering RNA (siRNA) causes sequence specific gene silencing of mRNA and has been shown to be a very promising therapeutic agent for a wide range of diseases.
Author: Alicia Gamboa
Abstract: Short interfering RNA (siRNA) causes sequence specific gene silencing of mRNA and has been shown to be a very promising therapeutic agent for a wide range of diseases. We have developed a hybrid collagen/cell penetrating peptide (CHP), that contains a triple helical domain (POG)n that provides stability, and a cell penetrating domain (Rn) which contains positively charged arginine residues allowing for internalization into cells. We determined that the CHPs form highly crystalline nanoparticles with siRNA with molar ratios of 1:18 and 1:9 depending on the number of arginines in the CPP domain. CHPs are able to effectively deliver and release siRNA into 3T3 Swiss mouse fibroblast cells with higher efficiency and gene silencing ability than that of Lipofectamine. The data suggest that our strategy for development of the CHP-siRNA complex can provide an avenue for effective delivery of siRNA.
Les peptides vecteurs (ou cell-penetrating peptides CPPs) ont émergé comme une nouvelle classe de transporteurs vers le milieu intracellulaire de macromolécules d'intérêt.
Author: Chérine Bechara
Les peptides vecteurs (ou cell-penetrating peptides CPPs) ont émergé comme une nouvelle classe de transporteurs vers le milieu intracellulaire de macromolécules d'intérêt. Néanmoins, et afin de mieux utiliser ces vecteurs, il faut en comprendre les mécanismes d'entrée ainsi que leur localisation finale dans les cellules. Dans ce contexte, mon travail vise à mieux comprendre les interactions moléculaires entre les CPPs basiques et les constituants de la membrane plasmique, qui pourront être impliqués dans l'internalisation de ces CPPs. Les différents résultats montrent qu'une meilleure affinité à la membrane plasmique d'un peptide ne corrèle pas avec une meilleure efficacité d'internalisation. Par ailleurs, les glycosaminoglycanes (GAGs) sont démontrés comme étant des acteurs important de l'endocytose des CPPs par agrégation des complexes CPPs/GAGs. La formation d'agrégats stables n'a été observée que pour les CPPs basiques qui comportent des résidus tryptophane dans leur séquence, qui se structurent en brin b suite à la complexation avec les GAGs. En absence de résidus tryptophane, un nombre critique de résidus arginine confère cependant aux séquences peptidiques des capacités d'internalisation similaires à celles des peptides avec tryptophane. Par ailleurs, l'hydrolyse de la sphingomyéline et la formation de domaines riches en céramide augmente l'entrée des CPPs dans les cellules sauvages plus que dans les cellules déficientes en GAGs. De plus, l'augmentation de l'entrée est plus marquée pour les peptides comprenant des résidus tryptophane, démontrant que la formation des domaines riches en céramide augmente l'endocytose des CPPs déclenchée par l'agrégation des GAGs.
MiRNAs are gene expression regulators with potential therapeutic applications.
Author: Gemma Carreras Badosa
MiRNAs are gene expression regulators with potential therapeutic applications. We have previously shown that miR-146a mimics and cell penetrating peptide (CPP) PepFect6 form noncovalent nanocomplexes, which suppress inflammation keratinocytes (KCs) and in a mouse model of irritant contact dermatitis. As in the skin, KCs, Langerhanu2019s cells and dermal dendritic cells (DCs) are main cell types exposed to therapeutic targeting, we here aimed to test the capacity of selected CPPs in delivery of miRNA mimics into KCs and in vitro differentiated DCs. We used PepFect (PF) and NickFect (NF) type of CPPs and show that they both support delivery of fluorescently labelled miRNA mimics into KCs and to a lesser extent to DCs. In KCs, the downregulation of miR-146a-influenced genes was evident with both PF and NF type peptides, while in DCs, only NF-delivered miR-146a was efficient in the suppression of the target genes. Any of the tested CPPs did not cause immune activation of DCs. Transmission electron microscopy analysis with nanogold labelled miR-146a mimics showed that in case of NFs, endocytosis is an active route of delivery in KCs and DCs. While in NF-miR-146a complexes were found mainly in endosomes and cytoplasm, the PF-miR-146a nanocomplexes were detected more often at the surface of DCs, indicating that they either enter poorly or are subjected to antigen presenting. In conclusion, NFs efficiently transport miRNA mimics into KCs and DCs and therefore may have advantage in therapeutic delivery of miRNAs. Further studies will be needed to test the efficiency of NF-miR146a nanocomplexes in skin inflammation in vivo.
22.214.171.124 Cationic cell-penetrating peptides CPP is the type of peptides that can
translocate the membrane and is widely used in intracellular drug delivery. These
peptides are constituted by 35 amino acids and possess positive charge on their
Publisher: Academic Press
The Future of Pharmaceutical Product Development and Research examines the latest developments in the pharmaceutical sciences, also highlighting key developments, research and future opportunities. Written by experts in the field, this volume in the Advances in Pharmaceutical Product Development and Research series deepens our understanding of the product development phase of drug discovery and drug development. Each chapter covers fundamental principles, advanced methodologies and technologies employed by pharmaceutical scientists, researchers and the pharmaceutical industry. The book focuses on excipients, radiopharmaceuticals, and how manufacturing should be conducted in an environment that follows Good Manufacturing Practice (GMP) guidelines. Researchers and students will find this book to be a comprehensive resource for those working in, and studying, pharmaceuticals, cosmetics, biotechnology, foods and related industries. Provides an overview of practical information for clinical trials Outlines how to ensure an environment that follows Good Manufacturing Practice (GMP) Examines recent developments and suggests future directions for drug production methods and techniques
This work details the recent advancements we have made to improve our high throughput technique, mRNA display, to yield more therapeutically relevant peptides to inhibit PPIs.
Author: Nicolas A. Abrigo
Peptides are emerging as promising therapeutics due to their inhibitory affinity towards protein-protein interactions (PPI). However, peptides have been limited mainly by their poor bio-stability and lack of cell permeability. Efforts to generate drug-like peptides have led to the development of macrocyclic peptides, which exhibit improved stability. Yet, most macrocyclic peptides still require the assistance of a cell penetrating peptide (CPP) for cellular entry. High throughput technologies have been exceptional tools for the discovery of peptides to interrupt PPIs. This work details the recent advancements we have made to improve our high throughput technique, mRNA display, to yield more therapeutically relevant peptides to inhibit PPIs. Our advancements are focused on cell permeability, protease stability, and secondary structure for enhanced affinity. Here we develop and optimize a cyclic CPP that can be included in future mRNA display libraries. We also tested the ability of our CPP to deliver an impermeable peptide cargo into cells. We rationally designed and tested linear and cyclic peptides to improve affinity to the BRCA1 protein. We used computational work to complement our experimental results for our CPPs and BRCA1 inhibitors. We examined peptides that arose from a library containing a mix of linear, monocyclic, and bicyclic peptides constructed using orthogonal cyclization chemistries. We rationally designed cyclic peptides and tested their affinity against Hsp70. We proposed a novel selection strategy to find optimal CPP motifs.
This book presents an interdisciplinary approach and general introduction to peptide science, covering contemporary topics including their applicability in therapeutics, peptide hormones, amyloid structures, self-assembled structures, ...
Author: Ian W. Hamley
Publisher: John Wiley & Sons
Provides an interdisciplinary introduction to peptide science, covering their properties and synthesis, as well as many contemporary applications Peptides are biomolecules comprised of amino acids which play an important role in modulating many physiological processes in our body. This book presents an interdisciplinary approach and general introduction to peptide science, covering contemporary topics including their applicability in therapeutics, peptide hormones, amyloid structures, self-assembled structures, hydrogels, and peptide conjugates including lipopeptides and polymer-peptide conjugates. In addition, it discusses basic properties and synthesis clearly and concisely. Taking a logical approach to the subject, Introduction to Peptide Science gives readers the fundamental knowledge that is required to understand the cutting-edge material which comes later in the book. It offers readers in-depth chapter coverage of the basic properties of peptides; synthesis; amyloid and peptide aggregate structures; antimicrobial peptides and cell-penetrating peptides; and peptide therapeutics and peptide hormones. Introduces readers to peptide science, including synthesis and properties Provides unique content covering properties, synthesis, self-assembly, aggregation, and applications Summarizes contemporary topics in an accessible fashion including applications in therapeutics, peptide hormones, amyloid structures, self-assembled structures, hydrogels, and peptide conjugates including lipopeptides Presented at an introductory level for the benefit of students and researchers who are new to the subject Introduction to Peptide Science is an ideal text for undergraduate students of chemistry, biochemistry, and other related biological subjects, and will be a valuable resource for postgraduate students and researchers involved in peptide science and its applications.
Therapeutic Proteins and Peptides, Volume 112 in an ongoing series promotes further research in the discovery of new therapeutic targets that can be affected by therapeutic proteins and peptides to cure or manage symptoms of human diseases, ...
Publisher: Academic Press
Therapeutic Proteins and Peptides, Volume 112 in an ongoing series promotes further research in the discovery of new therapeutic targets that can be affected by therapeutic proteins and peptides to cure or manage symptoms of human diseases, with this release focusing on the Rational Design of Stable Liquid Formulations of Biopharmaceuticals, Formulation strategies for peptides, proteins and antibodies using nanotechnology, the Solution structural dynamics of therapeutic peptides and their adsorption on plasmonic nanoparticles, Enzymatic approaches of protein-polymer conjugation, Chimeric small antibody fragments as a strategy to deliver therapeutic payloads, Smart cell-penetrating peptide-based techniques for cytoplasmic delivery of therapeutic macromolecules, and more. Describes advances in the discovery and application of therapeutic proteins/peptides which allow better targeting to the site of treatment and cause fewer adverse effects when compared to chemical compounds used for disease treatment Targeted to a very wide audience of specialists, researchers and students Written by well-renown authorities in their field Includes a number of high quality illustrations, figures and tables
A stepwise dissection of the intracellular fate of cationic cell - penetrating peptides . J. Biolog . Chem . 279 : 1262512635 . 64. Potocky T B , Menon A K ,
Gellman S H ( 2003 ) . Cytoplasmic and nuclear delivery of TAT - derived peptide
and a ...
Author: Shayne C. Gad
Describes the use of biotechnology to develop pharmaceuticals. This book gives the professional a basic tool to facilitate the development of biotech medicines by bringing together a general overview of biotechnology used in the drug development process, along with a compendium of regulations and validation methods.
A Comparative Study on the Cellular Uptake of different Cell - Penetrating Peptides Ulrike Krauss , Michael Stahl , Martin Müller and Annette G . Beck -
Sickinger Institute of Biochemistry , Faculty of Lifesciences , Pharmacy and
Author: Fundación Dr. Antonio Esteve. SymposiumPublish On: 2005
References [ 1 ] M . Lindgren , et al . , Cell - penetrating peptides 21 ( 3 ) ( 2000 )
99 - 1003 . [ 2 ] S . Futaki , et al . , Structural variety of membrane permeable
peptides , Current Protein and Peptide Science 4 ( 2 ) ( 2003 ) 87 - 96 . [ 3 ] S .
Author: Fundación Dr. Antonio Esteve. Symposium
Publisher: Elsevier Science Health Science Division
There are many potent drugs available for many diseases of the brain (e.g. Alzheimer's Disease, Parkinson's Disease, Multiple Sclerosis, Stroke, Brain tumors) The effectiviness however is not optimal since barriers in the brain prevent the drugs from reaching the brain in sufficient therapeutic concentrations (e.g. the blood-brain barrier and the blood-cerebrospinal fluid barrier). Drug Transport(ers) and the Diseased Brain contains the papers of a timely symposium held in Spain between 6 and 9 October 2004, which sets out not only the point of view of the academic researcher and the clinician, but also from the pharmaceutical industrial on how to overcome these barriers and how to treat brain diseases effectively. Blood-brain barrier and blood-cerebrospinal fluid-barrier drug transport; Drug targeting to the brain; Drug transporters at barriers in the brain