Evidence map›Paper›PMID 41911056›Full record

ArticleACS macro letters2026

Reversible, Polymeric Complexation of Therapeutic Peptides Using Esterification.

Aditi S Gourishankar, Mark S Bannon, Kelly M Bukovic, Earl Ashcraft, Laura M Pfitzer, Rachel A Letteri

Abstract read
In one paragraph

Article in ACS macro 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.

Aditi S GourishankarDepartment of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.
Mark S BannonDepartment of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.
Kelly M BukovicDepartment of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.ORCID 0009-0002-2060-7291
Earl AshcraftDepartment of Chemistry, University of Virginia, Charlottesville, Virginia 22903, United States.
Laura M PfitzerDepartment of Chemistry, University of Virginia, Charlottesville, Virginia 22903, United States.
Rachel A LetteriDepartment of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States.ORCID 0000-0002-2919-203X

Funding

Connexin-based Signaling in the Heart: Cellular and ExosomalR35HL161237 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI ROBERT G GOURDIE · 2022 to 2026
$4.4M
Optimizing therapeutic peptide presentation within polymersR35GM147424 · NIGMS · UNIVERSITY OF VIRGINIA · PI Rachel Letteri · 2022 to 2026
$1.8M
NHLBI NIH HHS R35 HL161237NIGMS NIH HHS R35 GM147424
6 · The paper itself

Abstract

Polyelectrolyte complexes permit the tunable, aqueous complexation of therapeutic peptides; however, their reliance on electrostatic and hydrophobic interactions limits complexation with weakly charged, hydrophilic peptides. While the peptide charge and hydrophobicity can be modified to encourage complexation, permanent modifications can hinder peptide activity and eventual release. Here, we show that esterifying the therapeutic peptide α-carboxyl terminus 11 (αCT11) reversibly increases its net charge and hydrophobicity, enabling complexation with anionic poly(methacrylic acid) and subsequent dissociation, as esters hydrolyze over 24 h. Prior to hydrolysis, hydrophobic aspartimide intermediates appear to promote aggregation, prolonging complexation. Further emphasizing the importance of hydrophobicity, replacing the aromatic polymer chain end with a less hydrophobic group abrogated complexation. Together, these studies showcase how esterification can be leveraged for reversible polymeric complexation of weakly charged, hydrophilic peptides and present exciting prospects for using polymer hydrophobicity to tune reversible complexation to meet patient and delivery method-specific needs.

Indexed as

PeptidesPolymersPolymethacrylic AcidsEsterificationHydrophobic and Hydrophilic InteractionsPeptidesPolymerspolymethacrylic acidPolymethacrylic Acids

Identifiers

PMID41911056
PMCPMC13104159

What OpenQuestion holds

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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.