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Record W2791142539 · doi:10.1002/pep2.24055

Stapled ghrelin peptides as fluorescent imaging probes

2018· article· en· W2791142539 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

VenuePeptide Science · 2018
Typearticle
Languageen
FieldNeuroscience
TopicRegulation of Appetite and Obesity
Canadian institutionsLawson Health Research InstituteCancer Care OntarioWestern University
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsGhrelinPeptideReceptorIn vivoChemistryLigand (biochemistry)LysineBiophysicsEx vivoFluorescenceBiochemistryIn vitroAmino acidBiology

Abstract

fetched live from OpenAlex

Abstract Fluorescently labelled ghrelin is an effective imaging probe for ex vivo biopsy analysis, in vivo distribution studies, and cell‐based analyses. The objective of our study was to improve the receptor affinity and stability of this ghrelin probe through cyclization, thereby providing a chemical probe with advantages in specificity and sensitivity as compared to immunohistochemical approaches. Truncation of ghrelin to its first 20 essential binding amino acids simplifies chemical synthesis, but reduces the α‐helical content of the peptide, which is important for receptor recognition. To overcome this limitation, we used a “staple scan” to synthesize stable α‐helical cyclic ghrelin(1‐20) analogues using a lactam bridge in either the i, i + 4 or i, i + 7 position. Stapling improved helicity in every case when compared to the linear sequence; however, the binding affinity to the receptor was dependent on the staple position. The peptide with the greatest improvement resulted in a [θ] 222 /[θ] 208 ratio of 0.84, and an IC 50 of 7.85 nM. The lead analogue was fluorescently labeled on the C‐terminal lysine of the peptide and microscopy experiments confirmed receptor binding in cells expressing GHS‐R1a. We postulate that the lead stapled peptide can be used as a cancer cell‐specific fluorescent stain with potential research and clinical applications.

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)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.033
Threshold uncertainty score0.998

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.002
Scholarly communication0.0000.001
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.003

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 head0.019
GPT teacher head0.290
Teacher spread0.271 · 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