Cited by 84Monoclonal and Polyclonal Antibodies ResearchBiochemical and Structural CharacterizationChemical Synthesis and Analysis

Target-Binding Proteins Based on the 10th Human Fibronectin Type III Domain (10Fn3)

Koide, Shohei, Koide, Akiko, Lipovšek, Daša·2012·Methods in Enzymology

Abstract

We describe concepts and methods for generating a family of engineered target-binding proteins designed on the scaffold of the 10th human fibronectin type III domain ((10)Fn3), an extremely stable, single-domain protein with an immunoglobulin-like fold but lacking disulfide bonds. Large libraries of possible target-binding proteins can be constructed on the (10)Fn3 scaffold by diversifying the sequence and length of its surface loops, which are structurally analogous to antibody complementarity-determining regions. Target-binding proteins with high affinity and specificity are selected from (10)Fn3-based libraries using in vitro evolution technologies such as phage display, mRNA display, or yeast-surface display. (10)Fn3-based target-binding proteins have binding properties comparable to those of antibodies, but they are smaller, simpler in architecture, and more user-friendly; as a consequence, these proteins are excellent building blocks for the construction of multidomain, multifunctional chains. The ease of engineering and robust properties of (10)Fn3-based target-binding proteins have been validated by multiple independent academic and industrial groups. In addition to performing well as specific in vitro detection reagents and research tools, (10)Fn3-based binding proteins are being developed as therapeutics, with the most advanced candidate currently in Phase II clinical trials.

Integrity signals

Registry

Crossref · 10.1016/b978-0-12-396962-0.00006-9

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Monomeric proteins based on the synthetic protein (FN3) skeleton are similar in function to antibodies and can be used in combination with the corresponding target; they have smaller molecular weight and clearer structure compared to traditional antibodies, and are more stable in oxidation/reduction conditions, making them a new type of ideal inhibitor.

    “Monomeric proteins, based on the synthetic protein (FN3) skeleton, are similar in function to antibodies and can be used in combination with the corresponding target. These proteins have a smaller molecular weight and clearer structure compared to traditional antibodies. Moreover, they are more stable in oxidation/reduction conditions, making them a new type of ideal inhibitor.330,331”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Koide, S., Koide, A., & Lipovšek, D.
Affiliations
  • University of Chicago (US)
  • Bristol-Myers Squibb (United States) (US)
Venue
Methods in Enzymology
Publisher
Elsevier
Published
2012
Volume
503
Pages
135-156
ISSN
0076-6879 (ISSN-L)
OpenAlex
W783708
Cited by
84
References
41
Citations by year
2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 8 · 2013: 6 · 2012: 6
FWCI
30.07
Type
book chapter
Language
en
Open access
closed
Locations
  • Methods in enzymology on CD-ROM/Methods in enzymology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of General Medical Sciences (R01GM090324, R01GM072688, U54GM087519)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
Keywords
fibronectin type III domain, single-domain proteins, immunoglobulin-like fold, phage display, mRNA display, yeast surface display, in vitro evolution, hypervariable region, therapeutic proteins, antibody mimics
MeSH terms
Antibodies, Carrier Proteins, Escherichia coli, Fibronectins, Humans, Plasmids, Recombinant Fusion Proteins, RNA, Messenger, Substrate Specificity, Yeasts, Protein Engineering, Drug Delivery Systems, Protein Folding, Peptide Library, Protein Sorting Signals, Complementarity Determining Regions, Protein Stability

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review