scholarly journals A novel, stable, helical scaffold as an alternative binder - construction of phage display libraries.

2012 ◽  
Vol 59 (3) ◽  
Author(s):  
Anna Cyranka-Czaja ◽  
Jacek Otlewski
Keyword(s):  
Phage Display ◽  
Measles Virus ◽  
In Vitro Selection ◽  
Biophysical Properties ◽  
Phage Display Technology ◽  
High Affinity ◽  
Promising Tool ◽  
Phage Display Libraries ◽  
Display Technology

Specific, high affinity binding macromolecules are of great importance for biomedical and biotechnological applications. The most popular classical antibody-based molecules have recently been challenged by alternative scaffolds with desirable biophysical properties. Phage display technology applied to such scaffolds allows generation of potent affinity reagents by in vitro selection. Here, we report identification and characterization of a novel helical polypeptide with advantageous biophysical properties as a template for construction of phage display libraries. A three-helix bundle structure, based on Measles virus phosphoprotein P shows a very favourable stability and solubility profile. We designed, constructed and characterized six different types of phage display libraries based on the proposed template. Their functional size of over 10(9) independent clones, balanced codon bias and decent display level are key parameters attesting to the quality and utility of the libraries. The new libraries are a promising tool for isolation of high affinity binders based on a small helical scaffold which could become a convenient alternative to antibodies.

scholarly journals Development of Anti-Infectives Using Phage Display: Biological Agents against Bacteria, Viruses, and Parasites

2012 ◽  
Vol 56 (9) ◽  
pp. 4569-4582 ◽  
Author(s):  
Johnny X. Huang ◽  
Sharon L. Bishop-Hurley ◽  
Matthew A. Cooper
Keyword(s):  
Phage Display ◽  
Significant Contribution ◽  
Biological Agents ◽  
Preclinical Development ◽  
Phage Display Technology ◽  
Whole Cells ◽  
Drug Candidates ◽  
Phage Display Libraries ◽  
Wide Range ◽  
Display Technology

ABSTRACTThe vast majority of anti-infective therapeutics on the market or in development are small molecules; however, there is now a nascent pipeline of biological agents in development. Until recently, phage display technologies were used mainly to produce monoclonal antibodies (MAbs) targeted against cancer or inflammatory disease targets. Patent disputes impeded broad use of these methods and contributed to the dearth of candidates in the clinic during the 1990s. Today, however, phage display is recognized as a powerful tool for selecting novel peptides and antibodies that can bind to a wide range of antigens, ranging from whole cells to proteins and lipid targets. In this review, we highlight research that exploits phage display technology as a means of discovering novel therapeutics against infectious diseases, with a focus on antimicrobial peptides and antibodies in clinical or preclinical development. We discuss the different strategies and methods used to derive, select, and develop anti-infectives from phage display libraries and then highlight case studies of drug candidates in the process of development and commercialization. Advances in screening, manufacturing, and humanization technologies now mean that phage display can make a significant contribution in the fight against clinically important pathogens.

scholarly journals Novel Blood–Brain Barrier Shuttle Peptides Discovered through the Phage Display Method

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 874 ◽  
Author(s):  
Petra Majerova ◽  
Jozef Hanes ◽  
Dominika Olesova ◽  
Jakub Sinsky ◽  
Emil Pilipcinec ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Phage Display ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Phage Display Technology ◽  
Blood Brain ◽  
Display Technology ◽  
The Brain

Delivery of therapeutic agents into the brain is a major challenge in central nervous system drug development. The blood–brain barrier (BBB) prevents access of biotherapeutics to their targets in the central nervous system and, therefore, prohibits the effective treatment of many neurological disorders. To find blood–brain barrier shuttle peptides that could target therapeutics to the brain, we applied a phage display technology on a primary endothelial rat cellular model. Two identified peptides from a 12 mer phage library, GLHTSATNLYLH and VAARTGEIYVPW, were selected and their permeability was validated using the in vitro BBB model. The permeability of peptides through the BBB was measured by ultra-performance liquid chromatography-tandem mass spectrometry coupled to a triple-quadrupole mass spectrometer (UHPLC-MS/MS). We showed higher permeability for both peptides compared to N–C reversed-sequence peptides through in vitro BBB: for peptide GLHTSATNLYLH 3.3 × 10−7 cm/s and for peptide VAARTGEIYVPW 1.5 × 10−6 cm/s. The results indicate that the peptides identified by the in vitro phage display technology could serve as transporters for the administration of biopharmaceuticals into the brain. Our results also demonstrated the importance of proper BBB model for the discovery of shuttle peptides through phage display libraries.

scholarly journals Phage Display Libraries for Antibody Therapeutic Discovery and Development

Antibodies ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 44 ◽  
Author(s):  
Juan C. Almagro ◽  
Martha Pedraza-Escalona ◽  
Hugo Iván Arrieta ◽  
Sonia Mayra Pérez-Tapia
Keyword(s):  
Phage Display ◽  
State Of The Art ◽  
Antibody Engineering ◽  
Phage Display Technology ◽  
Phage Display Libraries ◽  
Display Technology ◽  
Antibody Libraries ◽  
Antibody Repertoires ◽  
Remarkable Progress

Phage display technology has played a key role in the remarkable progress of discovering and optimizing antibodies for diverse applications, particularly antibody-based drugs. This technology was initially developed by George Smith in the mid-1980s and applied by John McCafferty and Gregory Winter to antibody engineering at the beginning of 1990s. Here, we compare nine phage display antibody libraries published in the last decade, which represent the state of the art in the discovery and development of therapeutic antibodies using phage display. We first discuss the quality of the libraries and the diverse types of antibody repertoires used as substrates to build the libraries, i.e., naïve, synthetic, and semisynthetic. Second, we review the performance of the libraries in terms of the number of positive clones per panning, hit rate, affinity, and developability of the selected antibodies. Finally, we highlight current opportunities and challenges pertaining to phage display platforms and related display technologies.

In vitro effect of a thrombin inhibition peptide selected by phage display technology

2002 ◽  
Vol 107 (6) ◽  
pp. 365-371 ◽  
Author(s):  
Muriel S Meiring ◽  
Derek Litthauer ◽  
Jolan Hársfalvi ◽  
Veronica van Wyk ◽  
Philip N Badenhorst ◽  
...  
Keyword(s):  
Phage Display ◽  
Phage Display Technology ◽  
Thrombin Inhibition ◽  
Display Technology ◽  
Vitro Effect

Recovery of High-Affinity Phage from a Nitrostreptavidin Matrix in Phage-Display Technology

1996 ◽  
Vol 243 (2) ◽  
pp. 264-269 ◽  
Author(s):  
Moshe Balass ◽  
Ely Morag ◽  
Edward A. Bayer ◽  
Sara Fuchs ◽  
Meir Wilchek ◽  
...  
Keyword(s):  
Phage Display ◽  
Phage Display Technology ◽  
High Affinity ◽  
Display Technology

scholarly journals Identification of Novel Single-Domain Antibodies against FGF7 Using Phage Display Technology

2017 ◽  
Vol 23 (2) ◽  
pp. 193-201
Author(s):  
Behzad Jafari ◽  
Maryam Hamzeh-Mivehroud ◽  
Ali A. Moosavi-Movahedi ◽  
Siavoush Dastmalchi
Keyword(s):  
Growth Factor ◽  
Phage Display ◽  
Fibroblast Growth Factor ◽  
Single Domain ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fibroblast Growth ◽  
Phage Display Technology ◽  
Display Technology ◽  
Single Domain Antibodies

Fibroblast growth factor 7 (FGF7) is a member of the fibroblast growth factor (FGF) family of proteins. FGF7 is of stromal origin and produces a paracrine effect on epithelial cells. In the current investigation, we aimed to identify new single-domain antibodies (sdAbs) against FGF7 using phage display technology. The vector harboring the codon-optimized DNA sequence for FGF7 protein was transformed into Escherichia coli BL21 (DE3) pLysS, and then the protein was expressed at the optimized condition. Enzyme-linked immunosorbent assay, circular dichroism spectropolarimetry, and in vitro scratch assay experiments were used to confirm the proper folding and functionality of the purified FGF7 protein. The purity of the produced FGF7 was 92%, with production yield of 3.5 mg/L of culture. Panning against the purified FGF7 was performed, and the identified single-domain antibodies showed significant affinity. Further investigation on one of the selected sdAb displaying phage clones showed concentration-dependent binding to FGF7. The selected sdAb can be used for developing novel tumor-suppressing agents where inhibition of FGF7 is required.

In vitro selection of a high affinity antibody to oestradiol using a phage display human antibody library

1996 ◽  
Vol 2 (3) ◽  
pp. 209-217 ◽  
Author(s):  
Anthony Pope ◽  
Kevin Pritchard ◽  
Andrew Williams ◽  
Andrew Roberts ◽  
John R. Hackett ◽  
...  
Keyword(s):  
Phage Display ◽  
In Vitro Selection ◽  
Human Antibody ◽  
Antibody Library ◽  
High Affinity ◽  
Selection Of
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