ArticleChembiochem : a European journal of chemical biology2008
Chemical and genetic wrappers for improved phage and RNA display.
Article in Chembiochem : a European journal of chemical biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Discovery of Macrocyclic Peptide Binders, Covalent Modifiers, and Degraders of a Structured RNA by mRNA Display.Journal of the American Chemical Society · 2025Article
- Engineering Phages to Fight Multidrug-Resistant Bacteria.Chemical reviews · 2025Review
- Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.Acta pharmaceutica Sinica. B · 2024Review
- Evolving a Peptide: Library Platforms and Diversification Strategies.International journal of molecular sciences · 2019Review
- Development of a Phage Display Panning Strategy Utilizing Crude Antigens: Isolation of MERS-CoV Nucleoprotein human antibodies.Scientific reports · 2019Article
- Guide to Selecting a Biorecognition Element for Biosensors.Bioconjugate chemistry · 2018Review
- Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.Nature communications · 2017Article
- Exploring the Secretomes of Microbes and Microbial Communities Using Filamentous Phage Display.Frontiers in microbiology · 2016Review
- Engineering chemically modified viruses for prostate cancer cell recognition.Molecular bioSystems · 2015Article
- Biosensing with Virus Electrode Hybrids.Current protocols in chemical biology · 2015Article
- Dual genetically encoded phage-displayed ligands.Analytical biochemistry · 2014Article
- Chemical modulation of M13 bacteriophage and its functional opportunities for nanomedicine.International journal of nanomedicine · 2014Review
- Sub-nanomolar detection of prostate-specific membrane antigen in synthetic urine by synergistic, dual-ligand phage.Journal of the American Chemical Society · 2013Article
- In vitro selection of proteins with desired characteristics using mRNA-display.Methods (San Diego, Calif.) · 2013Article
- In vitro evolution of enzymes.Methods in molecular biology (Clifton, N.J.) · 2013Article
- The scope of phage display for membrane proteins.Journal of molecular biology · 2011Article
- Hydrazide reactive peptide tags for site-specific protein labeling.Bioconjugate chemistry · 2011Article
- In vitro evolution of ligands to the membrane protein caveolin.Journal of the American Chemical Society · 2011Article
- Advantages of mRNA display selections over other selection techniques for investigation of protein-protein interactions.Expert review of proteomics · 2011Review
- Solubilization of a membrane protein by combinatorial supercharging.ACS chemical biology · 2011Article
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Authors and funding
8 authors.
Funding
Abstract
An Achilles heel inherent to all molecular display formats, background binding between target and display system introduces false positives into screens and selections. For example, the negatively charged surfaces of phage, mRNA, and ribosome display systems bind with unacceptably high nonspecificity to positively charged target molecules, which represent an estimated 35% of proteins in the human proteome. Here we report the first systematic attempt to understand why a broad class of molecular display selections fail, and then solve the underlying problem for both phage and RNA display. Firstly, a genetic strategy was used to introduce a short, charge-neutralizing peptide into the solvent-exposed, negatively charged phage coat. The modified phage (KO7(+)) reduced or eliminated nonspecific binding to the problematic high-pI proteins. In the second, chemical approach, nonspecific interactions were blocked by oligolysine wrappers in the cases of phage and total RNA. For phage display applications, the peptides Lys(n) (where n=16 to 24) emerged as optimal for wrapping the phage. Lys(8), however, provided effective wrappers for RNA binding in assays against the RNA binding protein HIV-1 Vif. The oligolysine peptides blocked nonspecific binding to allow successful selections, screens, and assays with five previously unworkable protein targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.