Evidence map›Paper›PMID 25234472›Full record

ArticleScientific reports2014

Serum stable natural peptides designed by mRNA display.

Shannon M Howell, Stephen V Fiacco, Terry T Takahashi, Farzad Jalali-Yazdi, Steven W Millward, Biliang Hu, Pin Wang, Richard W Roberts

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. 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
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Biosynthetic Strategies for Macrocyclic Peptides.Molecules (Basel, Switzerland) · 2021
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  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

8 authors at 2 institutions in 1 country.

Shannon M HowellDepartment of Chemistry, University of Southern California, Los Angeles, California 90089, United States.
Stephen V FiaccoDepartment of Chemistry, University of Southern California, Los Angeles, California 90089, United States.
Terry T TakahashiDepartment of Chemistry, University of Southern California, Los Angeles, California 90089, United States.
Farzad Jalali-YazdiMork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles CA, 90089-1211.
Steven W MillwardDepartment of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center, Houston, TX.
Biliang HuMork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles CA, 90089-1211.
Pin WangMork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles CA, 90089-1211.
Richard W Roberts1] Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States [2] Mork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles CA, 90089-1211.
University of Southern California · USThe University of Texas MD Anderson Cancer Center · 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
Polypeptide Design with Proteomic Scope via Microfluidic mRNA DisplayR01AI085583 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERTS, RICHARD W, SOH, HYONGSOK TOM · 2009 to 2013
$2.4M
SUPR Peptides to Inhibit Undruggable Cancer Target (PQ18)R01CA170820 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ROBERTS, RICHARD W, TAKAHASHI, TERRY TORAO · 2012 to 2015
$1.8M
NCI NIH HHS 5R01CA170820NCI NIH HHS R01 CA170820NIAID NIH HHS 5R01AI085583NIAID NIH HHS R01 AI085583NIGMS NIH HHS GM R01 60416
6 · The paper itself

Abstract

Peptides constructed with the 20 natural amino acids are generally considered to have little therapeutic potential because they are unstable in the presence of proteases and peptidases. However, proteolysis cleavage can be idiosyncratic, and it is possible that natural analogues of functional sequences exist that are highly resistant to cleavage. Here, we explored this idea in the context of peptides that bind to the signaling protein Gαi1. To do this, we used a two-step in vitro selection process to simultaneously select for protease resistance while retaining function-first by degrading the starting library with protease (chymotrypsin), followed by positive selection for binding via mRNA display. Starting from a pool of functional sequences, these experiments revealed peptides with 100-400 fold increases in protease resistance compared to the parental library. Surprisingly, selection for chymotrypsin resistance also resulted in similarly improved stability in human serum (~100 fold). Mechanistically, the decreases in cleavage results from both a lower rate of cleavage (kcat) and a weaker interaction with the protease (Km). Overall, our results demonstrate that the hydrolytic stability of functional, natural peptide sequences can be improved by two orders of magnitude simply by optimizing the primary sequence.

Indexed as

Peptide LibraryAmino Acid SequenceBlood ProteinsHumansPeptide HydrolasesPeptidesProtein BindingProteolysisRNA, MessengerBlood ProteinsPeptide HydrolasesPeptide LibraryPeptidesRNA, Messenger

Identifiers

PMID25234472
PMCPMC4168267
OpenAlexW2091245340

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.