Evidence map›Paper›PMID 17894440›Full record

ArticleACS chemical biology2007

Design of cyclic peptides that bind protein surfaces with antibody-like affinity.

Steven W Millward, Stephen Fiacco, Ryan J Austin, Richard W Roberts

Abstract read
In one paragraph

Article in ACS chemical biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 136 citations in OpenAlex.

  1. Article
  2. Review
  3. Design, synthesis, and analysis of macrobicyclic peptides for targeting the Gαi protein.Journal of peptide science : an official publication of the European Peptide Society · 2024
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
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  15. Article
  16. Article
  17. Mammalian Expression andACS omega · 2020
    Article
  18. Article
  19. ACS synthetic biology · 2020
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Steven W MillwardDivision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Stephen Fiacco
Ryan J Austin
Richard W Roberts
University of Southern California · USCalifornia Institute of Technology · US

Funding

IN VITRO SELECTION OF PROTEINS VIA MRNA-PROTEIN FUSIONSR01GM060416 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERTS, RICHARD W · 2000 to 2010
$2.9M
Implementation and Testing of PURE mRNA DisplayR21GM076678 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERTS, RICHARD W · 2006 to 2007
$442k
NIGMS NIH HHS GM R01 60416NIGMS NIH HHS R01 GM060416NIGMS NIH HHS R21 GM076678NIGMS NIH HHS R21 GM 76678
6 · The paper itself

Abstract

There is a pressing need for new molecular tools to target protein surfaces with high affinity and specificity. Here, we describe cyclic messenger RNA display with a trillion-member covalent peptide macrocycle library. Using this library, we have designed a number of high-affinity, redox-insensitive, cyclic peptides that target the signaling protein G alpha i1. In addition to cyclization, our library construction took advantage of an expanded genetic code, utilizing nonsense suppression to insert N-methylphenylalanine as a 21st amino acid. The designed macrocycles exhibit several intriguing features. First, the core motif seen in all of the selected variants is the same and shares an identical context with respect to the macrocyclic scaffold, consistent with the idea that selection simultaneously optimizes both the cyclization chemistry and the structural placement of the binding epitope. Second, detailed characterization of one molecule, cyclic G alpha i binding peptide (cycGiBP), demonstrates substantially enhanced proteolytic stability relative to that of the parent linear molecule. Third and perhaps most important, the cycGiBP peptide binds the target with very high affinity ( K i approximately 2.1 nM), similar to those of many of the best monoclonal antibodies and higher than that of the betagamma heterodimer, an endogenous G alpha i1 ligand. Overall the work provides a general route to design novel, low-molecular-weight, high-affinity ligands that target protein surfaces.

Indexed as

Amino Acid MotifsAntibody AffinityGTP-Binding Protein alpha SubunitsModels, MolecularPeptide LibraryPeptides, CyclicProtein BindingProtein EngineeringGTP-Binding Protein alpha SubunitsPeptide LibraryPeptides, Cyclic

Identifiers

PMID17894440
PMCPMC3747972
OpenAlexW2138567388

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.