Evidence map›Paper›PMID 34211593›Full record

ArticlePolymer chemistry2021

Synthesis of Disulfide-Bridging Trehalose Polymers for Antibody and Fab Conjugation Using a Bis-Sulfone ATRP Initiator.

Neil L Forsythe, Heather D Maynard

Open access · greenAbstract read
In one paragraph

Article in Polymer chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 39% 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

4 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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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

2 authors at 1 institution in 1 country.

Neil L ForsytheDepartment of Chemistry and Biochemistry and California NanoSystems Institute, 607 Charles E. Young Drive East, University of California, Los Angeles, CA 90095-1569.
Heather D MaynardDepartment of Chemistry and Biochemistry and California NanoSystems Institute, 607 Charles E. Young Drive East, University of California, Los Angeles, CA 90095-1569.
California NanoSystems Institute · US

Funding

CHEMISTRY BIOLOGY INTERFACE TRAINING PROGRAMT32GM008496 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYNARD, HEATHER D · 1993 to 2019
$6.3M
Trehalose Glycopolymers to Enhance both Pharmacokinetics and Stability of Therapeutic ProteinsR01EB020676 · NIBIB · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAYNARD, HEATHER D · 2016 to 2019
$1.3M
NIBIB NIH HHS R01 EB020676NIGMS NIH HHS T32 GM008496
6 · The paper itself

Abstract

Antibodies and antigen binding fragments (FABs) are widely used as therapeutics and conjugated polymers can enhance the properties of these important biomolecules. However, limitations to the selectivity and stability of current conjugation methodologies can inhibit the exploration of new antibody-polymer conjugates. Herein, we describe a new strategy for the synthesis of these conjugates that forms a stable thioether bond and can be directly incorporated into an atom transfer radical polymerization (ATRP) initiator. Specifically, a bis-sulfone alkyl bromide initiator was synthesized and utilized in the activators generated by electron transfer (AGET) ATRP of ethylene glycol methacrylate and trehalose methacrylate to form the respective polymers. The trehalose polymer was then irreversibly inserted into the disulfide bonds of Herceptin and Herceptin FAB after mild reduction to form the conjugates with quantitative conversions as verified by Western Blot and mass spectrometry after cleavage of the polymer. The binding of the Herceptin and Herceptin Fab conjugates to the receptor was investigated by indirect ELISA (enzyme-linked immunosorbent assay) and the EC50's were 0.90 and 2.74 nM, respectively, compared to Herceptin (0.26 nM) and the Fab (0.56 nM). The conjugates were subjected to heating studies at a constant 75 °C, the temperature determined in a heat ramp to be the threshold of stability for the antibody and FAB; the trehalose polymer was found to considerably increase the thermal stability of both Herceptin and Herceptin Fab. This work provides a new way to prepare polymer-antibody/Fab conjugates utilizing bis-sulfone end groups installed by atom transfer radical polymerization of the functionalized initiators and a way to stabilize these important molecules by conjugation to trehalose polymers.

Identifiers

PMID34211593
PMCPMC8240515
OpenAlexW3130979586

What OpenQuestion holds

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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.