Evidence map›Paper›PMID 33750839›Full record

ArticleNature communications2021

Lasso-grafting of macrocyclic peptide pharmacophores yields multi-functional proteins.

Emiko Mihara, Satoshi Watanabe, Nasir K Bashiruddin, Nozomi Nakamura, Kyoko Matoba, Yumi Sano, Rumit Maini, Yizhen Yin, Katsuya Sakai, Takao Arimori and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

18 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. RaPID Selection of Backbone Macrocyclic Peptides Targeting Akt2.Angewandte Chemie (International ed. in English) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Lasso-grafted designer cytokines.Nature biomedical engineering · 2023
    Article
  12. Article
  13. Review
  14. Genomic Insight intoBioengineering (Basel, Switzerland) · 2022
    Article
  15. Review
  16. Review
  17. Article
  18. 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

13 authors at 3 institutions in 1 country.

Emiko MiharaLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.ORCID 0000-0002-9127-8643
Satoshi WatanabeLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
Nasir K BashiruddinDepartment of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Nozomi NakamuraLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
Kyoko MatobaLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.
Yumi SanoLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.ORCID 0000-0002-4598-1557
Rumit MainiDepartment of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Yizhen YinDepartment of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Katsuya SakaiDivision of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID 0000-0002-0443-1786
Takao ArimoriLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan.ORCID 0000-0002-6063-5572
Kunio MatsumotoDivision of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID 0000-0002-6532-4482
Hiroaki SugaDepartment of Chemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan. hsuga@chem.s.u-tokyo.ac.jp.ORCID 0000-0002-5298-9186
Junichi TakagiLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, Osaka, Japan. takagi@protein.osaka-u.ac.jp.ORCID 0000-0002-1219-475X
Protein Research Foundation · JPThe University of Tokyo · JPKanazawa University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein engineering has great potential for devising multifunctional recombinant proteins to serve as next-generation protein therapeutics, but it often requires drastic modifications of the parental protein scaffolds e.g., additional domains at the N/C-terminus or replacement of a domain by another. A discovery platform system, called RaPID (Random non-standard Peptides Integrated Discovery) system, has enabled rapid discovery of small de novo macrocyclic peptides that bind a target protein with high binding specificity and affinity. Capitalizing on the optimized binding properties of the RaPID-derived peptides, here we show that RaPID-derived pharmacophore sequences can be readily implanted into surface-exposed loops on recombinant proteins and maintain both the parental peptide binding function(s) and the host protein function. We refer to this protein engineering method as lasso-grafting and demonstrate that it can endow specific binding capacity toward various receptors into a diverse set of scaffolds that includes IgG, serum albumin, and even capsid proteins of adeno-associated virus, enabling us to rapidly formulate and produce bi-, tri-, and even tetra-specific binder molecules.

Indexed as

Capsid ProteinsCarrier ProteinsCell LineDependovirusHumansImmunoglobulin GModels, MolecularPeptidesProtein EngineeringSerum AlbuminSmall Molecule LibrariesCapsid ProteinsCarrier ProteinsImmunoglobulin GPeptidesSerum AlbuminSmall Molecule Libraries

Identifiers

PMID33750839
PMCPMC7943567
OpenAlexW3114510610

What OpenQuestion holds

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LicenceCC BY
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.