Evidence map›Paper›PMID 41197881›Full record

ArticleBioorganic & medicinal chemistry letters2026

Identification of affinity-optimized peptide binders of a viral protease for chemical genetic applications.

Fernando Banales-Mejia, Emily M Dieter, Kyler J Radmall, Glenna W Foight, Douglas M Fowler, Dustin J Maly

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

6 authors.

Fernando Banales-MejiaDepartment of Chemistry, University of Washington, Seattle, WA, USA; Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA, USA.
Emily M DieterDepartment of Chemistry, University of Washington, Seattle, WA, USA.
Kyler J RadmallDepartment of Chemistry, University of Washington, Seattle, WA, USA.
Glenna W FoightDepartment of Chemistry, University of Washington, Seattle, WA, USA.
Douglas M FowlerDepartment of Genome Sciences, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA.
Dustin J MalyDepartment of Chemistry, University of Washington, Seattle, WA, USA; Department of Biochemistry, University of Washington, Seattle, WA, USA. Electronic address: djmaly@uw.edu.

Funding

New Molecular Probes For Protein KinasesR01GM086858 · NIGMS · UNIVERSITY OF WASHINGTON · PI MALY, DUSTIN J · 2008 to 2025
$5.5M
Leica SP8 WWL Confocal MicroscopeS10OD016240 · OD · UNIVERSITY OF WASHINGTON · PI CATTERALL, WILLIAM A · 2014 to 2014
$581k
Developing a Chemically-Controlled RAS ToolsetF31GM155953 · NIGMS · UNIVERSITY OF WASHINGTON · PI BANALES MEJIA, FERNANDO · 2024 to 2025
$90k
NIGMS NIH HHS F31 GM155953NIGMS NIH HHS R01 GM086858NIH HHS S10 OD016240
6 · The paper itself

Abstract

Chemically-controlled genetic tools are useful for studying biological systems due to their ability to dose-dependently and temporally modulate intracellular function. Chemically-disrupted proximity (CDP) systems, which involve the pre-localization of two interacting protein components that can be disrupted with a small molecule, are complementary to more commonly used chemically-inducible dimerization (CID) systems. However, fewer CDP systems have been developed, and the genetically-encoded protein components have not been as optimized for intracellular applications. Here, we describe a transcriptional activation reporter assay for screening the intracellular interaction between the 21-amino acid peptide ANR and HCVp NS3a, which are the genetically-encoded components of a CDP system that utilizes clinically-approved antiviral drugs. We used this assay to screen a library of single amino acid substitution ANR variants and identified several that increase the intracellular interaction between ANR and NS3a. By combining affinity-optimized single substitutions, we achieved improved transcriptional activation and engineered an autoinhibited signaling switch with low basal activity. Together, our study describes a functional assay for screening genetically-encoded CDP components and a more optimized version of ANR for intracellular applications.

Indexed as

HepacivirusPeptidesViral Nonstructural ProteinsAntiviral AgentsDEAD-box RNA HelicasesHumansMolecular StructureNucleoside-TriphosphataseSerine EndopeptidasesViral ProteasesAntiviral AgentsDEAD-box RNA HelicasesNS3 protein, hepatitis C virusNucleoside-TriphosphatasePeptidesSerine EndopeptidasesViral Nonstructural ProteinsViral ProteasesAutoinhibitionNS3a proteasePeptide binderProtein-peptide interactionRas signalingTranscriptional reporter

Identifiers

PMID41197881
PMCPMC12619934

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Registered trials

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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.