Issue 21, 2025

PVAylation: precision end-functionalized poly(vinyl alcohol) for site-selective bioconjugation

Abstract

The (bio)conjugation of polymers onto proteins enhances their pharmacokinetics and stability, most commonly using PEG (polyethylene glycol), but there is a need for alternatives. Poly(vinyl alcohol), PVA, is a water-soluble, biocompatible and environmentally degradable polymer, which also has the unique function of ice recrystallisation inhibition (IRI) which can aid the cryopreservation of biologics. Site-specific PVA bioconjugation (“PVAylation”) is underexplored due to the challenge of obtaining homogenous mono end-functional PVA. Here we show that following deprotection of the acetate (from the precursor poly(vinyl acetate)), the concurrent xanthate end-group reduction leads to a diversity of ambiguous end-groups which prevented precision conjugation. This is overcome by using a photo-catalyzed reduction of the omega-terminal xanthates to C–H, which is orthogonal to active-ester bioconjugation functionality at the alpha-chain terminus, demonstrated by MALDI-TOF mass spectrometry. This strategy enabled the preparation of well-defined mono-functional PVA displaying alkyne, biotin and O6-benzylguanine chain-end functionalities, which are each then used for covalent or non-covalent site-specific modification of three model proteins, introduce ice-binding function. These results will enable the synthesis of new bioconjugates containing PVA and be of particular benefit for low-temperature applications.

Graphical abstract: PVAylation: precision end-functionalized poly(vinyl alcohol) for site-selective bioconjugation

Supplementary files

Article information

Article type
Edge Article
Submitted
28 Jan 2025
Accepted
14 Apr 2025
First published
24 Apr 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2025,16, 9264-9275

PVAylation: precision end-functionalized poly(vinyl alcohol) for site-selective bioconjugation

D. E. Soutar, H. F. Mack, M. Ligorio, A. Bissoyi, A. N. Baker and M. I. Gibson, Chem. Sci., 2025, 16, 9264 DOI: 10.1039/D5SC00772K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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