Engineered proteins as specific binding reagents

Binz, Hans; Plückthun, Andreas

doi:10.1016/j.copbio.2005.06.005

Cited by 140 publications

(100 citation statements)

References 82 publications

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“…6 shows that the BsAb inhibit both mPDGFR␣ and mVEGFR2 from binding to their respective ligand, PDGF-AA and VEGF. The IC 50 of the BsAb for blocking mPDGFR␣/PDGF-AA is ϳ24 nM, compared with that of 2.7 nM for 1F2-CH/CL. On the other hand, the IC 50 values for blocking the mVEGFR2/VEGF interaction are ϳ13.5 and 3.5 nM for 1F2-2B4IgG and 2B4 IgG, respectively (Fig.…”

Section: Identification Of Single Vh Domain Antibodies To Mpdgfr␣ Fromentioning

confidence: 99%

“…The mixture was then transferred to 96-well plates precoated with rhPDGF-AA or VEGF (0.5 g/ml) and incubated at room temperature for 1 h. After washing three times, the plates were incubated with an anti-human Fc antibody-HRP conjugate and developed as described above. IC 50 , the antibody concentration that yielded 50% blockade of mPDGFR␣ or mVEGFR2 from binding to its respective ligand, was determined.…”

Section: Construction Of Bispecific Anti-mpdgfr␣ ϫ Anti-mvegfr2 Antibmentioning

confidence: 99%

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Single Variable Domain-IgG Fusion

Shen¹,

Vil²,

Jimenez³

et al. 2006

Journal of Biological Chemistry

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Section: Identification Of Single Vh Domain Antibodies To Mpdgfr␣ Fromentioning

confidence: 99%

Section: Construction Of Bispecific Anti-mpdgfr␣ ϫ Anti-mvegfr2 Antibmentioning

confidence: 99%

Single Variable Domain-IgG Fusion

Shen¹,

Vil²,

Jimenez³

et al. 2006

Journal of Biological Chemistry

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“…119,120 Phage display approaches generally enrich for an immobilized protein of interest and a complicated immunization protocol is not necessary. Results in this area are tabulated (Table 4) and discussed in this section.…”

Section: Targeting Amyloid With In Vitro Selected Peptides and Proteinsmentioning

confidence: 99%

Molecules that Target beta‐Amyloid

2007

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The devastating effects of Alzheimer’s and related amyloidogenic diseases have inspired the synthesis and evaluation of numerous ligands to understand the molecular mechanism of the aggregation of the beta‐amyloid peptide. Our review focuses on the current knowledge in this field with respect to molecules that have been demonstrated to interact with either oligomeric or fibrillar forms of the beta‐amyloid peptide. We describe natural proteins, peptides, peptidomimetics, and small molecules that have been found to interfere with beta‐amyloid aggregation. We also detail recent efforts in selecting molecules that target beta‐amyloid isolated from antibody, protein, and peptide libraries. These new molecules will likely aid in deciphering the details of the aggregation pathway for the beta‐amyloid peptide and provide reagents that may stabilize relevant oligomeric intermediates which likely have bearing on the pathophysiology of Alzheimer’s disease. Moreover, the described anti‐amyloid molecular toolbox will also provide an avenue for designing new diagnostic and therapeutic reagents.

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“…For therapeutics, high stability and low immunogenicity are essential, and synthetic antibodies libraries can be designed to directly supply molecules with these characteristics. Also, natural antibodies do not function intracellularly but it is possible to produce synthetic ''intrabodies'' or alternative scaffolds that are adapted for folding and function inside cells [8]. Recombinant antibodies are also modular, because they can be fused genetically to additional domains to endow additional functions, such as fluorescence to track protein localization and trafficking.…”

Section: Introductionmentioning

confidence: 99%

“…The combination of display technologies with structure-based design has enabled the development of ''synthetic'' antibody libraries with man-made antigen-binding sites and libraries built with alternative, non-antibody scaffolds [7,8]. Synthetic repertoires circumvent the need for natural antibodies altogether and possess advantages due to their highly defined nature.…”

Section: Introductionmentioning

confidence: 99%

Antibodies for all: The case for genome‐wide affinity reagents

Sidhu

2012

FEBS Letters

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a b s t r a c tFor more than 30 years, the production of research antibodies has been dominated by hybridoma technologies, while modern recombinant technologies have lagged behind. Here I discuss why this situation must change if we are to generate reliable, comprehensive reagent sets on a genome-wide scale, and I describe how a cultural shift in the research community could revolutionize and modernize the affinity reagent field. In turn, such a revolution would pay huge dividends by closing the gap between basic research and therapeutic development, thus enabling the development of myriad new therapies for unmet medical needs.Ó 2012 Federation of European Biochemical Societies. Published by Elsevier B.V.In most respects, the human genome project has been a resounding success. As a direct result of the initiative, not only do we have access to the complete human genome, as importantly, sequencing technologies have advanced to the point where whole genome sequencing has become a daily affair. Moreover, the astounding advances in DNA sequencing technology have dovetailed with, and often driven, the development of numerous other technologies for the systematic analysis of genomes, transcriptomes and proteomes. Consequently these are best of times for life scientists engaged in basic research. Our basic knowledge of the cell far exceeds what we imagined even a decade ago, and we have the tools to expand this knowledge almost infinitely within the spheres of established technologies.However, a fundamental tenet of the human genome project was that a complete view of the genome would open up myriad new avenues for therapy. Unfortunately, in this crucial aspect, the promise of the genomics era has not been fulfilled. More than a decade after completion of the genome, the drug development industry has not benefitted greatly from the explosion of basic knowledge, and in fact, the development of novel therapies has declined over this period. Thus, these are the worst of times for researchers engaged in drug discovery. The benefits of genomics and systems biology have not penetrated to the level of drug development and there is no obvious path forward for integrating this wealth of basic knowledge into the practical demands of drug development.Here, I focus on one problem that has contributed to the vast divide between the promise of genomics and the reality of drug development: the wide gap between the advanced tools for the manipulation of nucleic acids and the relatively primitive tools for manipulation of proteins. Proteins are central to the control of virtually all cellular processes, and virtually all drugs act by modulating the activities of proteins. Thus, it is reasonable to propose that the translation of genomic knowledge to therapeutic development will require a toolkit that enables the manipulation of proteins with the same speed and precision that is commonplace for the manipulation of DNA and RNA. Ideally, this toolkit would be comprehensive, providing us with tools that could track, localize, and modulate ...

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Engineered proteins as specific binding reagents

Cited by 140 publications

References 82 publications

Single Variable Domain-IgG Fusion

Single Variable Domain-IgG Fusion

Molecules that Target beta‐Amyloid

Antibodies for all: The case for genome‐wide affinity reagents

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