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Record W2902197007 · doi:10.2147/dddt.s186614

Synthesis of small peptide compounds, molecular docking, and inhibitory activity evaluation against phosphatases PTP1B and SHP2

2018· article· en· W2902197007 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueDrug Design Development and Therapy · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Tyrosine Phosphatases
Canadian institutionsUniversity of Alberta
FundersNatural Sciences and Engineering Research Council of CanadaAllard Foundation
KeywordsAllosteric regulationBiochemistryPhosphataseDocking (animal)PeptideChemistryEnzymeProtein tyrosine phosphataseActive siteTripeptideBinding siteIC50In vitro

Abstract

fetched live from OpenAlex

Background: The protein tyrosine phosphatases PTP1B and SHP2 are promising drug targets in treatment design for breast cancer. Searching for specific inhibitors of their activity has recently become the challenge of many studies. Previous work has indicated that the promising PTP inhibitors may be small compounds that are able to bind and interact with amino residues from the binding site. Purpose: The main goal of our study was to synthesize and analyze the effect of selected small peptide inhibitors on oncogenic PTP1B and SHP2 enzymatic activity and viability of MCF7 breast cancer cells. We also performed computational analysis of peptides binding with allosteric sites of PTP1B and SHP2 phosphatases. Methods: We measured the inhibitory activity of compounds utilizing recombinant enzymes and MCF7 cell line. Computational analysis involved docking studies of binding conformation and interactions of inhibitors with allosteric sites of phosphatases. Results: The results showed that the tested compounds decrease the enzymatic activity of phosphatases PTP1B and SHP2 with IC 50 values in micromolar ranges. We observed higher inhibitory activity of dipeptides than tripeptides. Phe-Asp was the most effective against SHP2 enzymatic activity, with IC 50 =5.2±0.4 µM. Micromolar concentrations of tested dipeptides also decreased the viability of MCF7 breast cancer cells, with higher inhibitory activity observed for the Phe-Asp peptide. Moreover, the peptides tested were able to bind and interact with allosteric sites of PTP1B and SHP2 phosphatases. Conclusion: Our research showed that small peptide compounds can be considered for the design of specific inhibitors of oncogenic protein tyrosine phosphatases. Keywords: breast cancer, protein tyrosine phosphatase PTP1B, SHP2, peptides, PTP inhibitors

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.310
Threshold uncertainty score0.751

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.024
GPT teacher head0.250
Teacher spread0.226 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it