Comb poly(oligo(2-ethyl-2-oxazoline)methacrylate)-peptide conjugates prepared by aqueous Cu(0)-mediated polymerization and reductive amination

Jennifer Collins, Sacha J. Wallis, Alexandre Simula, Michael R. Whittaker, Michelle P. McIntosh, Paul Wilson, Thomas P. Davis, David M. Haddleton, Kristian Kempe

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

The controlled synthesis of poly(oligo(2-ethyl-2-oxazoline)methacrylate) (P(OEtOxMA)) polymers by Cu(0)-mediated polymerization in water/methanol mixtures is reported. Utilizing an acetal protected aldehyde initiator for the polymerization, well-defined polymers are synthesized (>99% conversion, (Eth) < 1.25) with subsequent postpolymerization deprotection resulting in α-aldehyde end group containing comb polymers. These P(OEtOxMA) are subsequently site-specifically conjugated, via reductive amination, to a dipeptide (NH2-Gly-Tyr-COOH) as a model peptide, prior to conjugation to the functional peptide oxytocin. The resulting oxytocin conjugates are evaluated in comparison to poly(oligo(ethylene glycol) methyl ether methacrylate) combs synthesized in the same manner for potential effects on thermal stability in comparison to the native peptide.

Original languageEnglish
Article number1600534
Number of pages7
JournalMacromolecular Rapid Communications
Volume38
Issue number2
DOIs
Publication statusPublished - 1 Jan 2017

Keywords

  • Controlled radical polymerization
  • Oxytocin
  • Poly(2-oxazoline)
  • Polymer-peptide conjugation
  • Reductive amination

Cite this

@article{898bddf6600b4b7996d112d313d4ec57,
title = "Comb poly(oligo(2-ethyl-2-oxazoline)methacrylate)-peptide conjugates prepared by aqueous Cu(0)-mediated polymerization and reductive amination",
abstract = "The controlled synthesis of poly(oligo(2-ethyl-2-oxazoline)methacrylate) (P(OEtOxMA)) polymers by Cu(0)-mediated polymerization in water/methanol mixtures is reported. Utilizing an acetal protected aldehyde initiator for the polymerization, well-defined polymers are synthesized (>99{\%} conversion, (Eth) < 1.25) with subsequent postpolymerization deprotection resulting in α-aldehyde end group containing comb polymers. These P(OEtOxMA) are subsequently site-specifically conjugated, via reductive amination, to a dipeptide (NH2-Gly-Tyr-COOH) as a model peptide, prior to conjugation to the functional peptide oxytocin. The resulting oxytocin conjugates are evaluated in comparison to poly(oligo(ethylene glycol) methyl ether methacrylate) combs synthesized in the same manner for potential effects on thermal stability in comparison to the native peptide.",
keywords = "Controlled radical polymerization, Oxytocin, Poly(2-oxazoline), Polymer-peptide conjugation, Reductive amination",
author = "Jennifer Collins and Wallis, {Sacha J.} and Alexandre Simula and Whittaker, {Michael R.} and McIntosh, {Michelle P.} and Paul Wilson and Davis, {Thomas P.} and Haddleton, {David M.} and Kristian Kempe",
year = "2017",
month = "1",
day = "1",
doi = "10.1002/marc.201600534",
language = "English",
volume = "38",
journal = "Macromolecular Rapid Communications",
issn = "1022-1336",
publisher = "H{\"u}thig & Wepf Verlag",
number = "2",

}

Comb poly(oligo(2-ethyl-2-oxazoline)methacrylate)-peptide conjugates prepared by aqueous Cu(0)-mediated polymerization and reductive amination. / Collins, Jennifer; Wallis, Sacha J.; Simula, Alexandre; Whittaker, Michael R.; McIntosh, Michelle P.; Wilson, Paul; Davis, Thomas P.; Haddleton, David M.; Kempe, Kristian.

In: Macromolecular Rapid Communications, Vol. 38, No. 2, 1600534, 01.01.2017.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Comb poly(oligo(2-ethyl-2-oxazoline)methacrylate)-peptide conjugates prepared by aqueous Cu(0)-mediated polymerization and reductive amination

AU - Collins, Jennifer

AU - Wallis, Sacha J.

AU - Simula, Alexandre

AU - Whittaker, Michael R.

AU - McIntosh, Michelle P.

AU - Wilson, Paul

AU - Davis, Thomas P.

AU - Haddleton, David M.

AU - Kempe, Kristian

PY - 2017/1/1

Y1 - 2017/1/1

N2 - The controlled synthesis of poly(oligo(2-ethyl-2-oxazoline)methacrylate) (P(OEtOxMA)) polymers by Cu(0)-mediated polymerization in water/methanol mixtures is reported. Utilizing an acetal protected aldehyde initiator for the polymerization, well-defined polymers are synthesized (>99% conversion, (Eth) < 1.25) with subsequent postpolymerization deprotection resulting in α-aldehyde end group containing comb polymers. These P(OEtOxMA) are subsequently site-specifically conjugated, via reductive amination, to a dipeptide (NH2-Gly-Tyr-COOH) as a model peptide, prior to conjugation to the functional peptide oxytocin. The resulting oxytocin conjugates are evaluated in comparison to poly(oligo(ethylene glycol) methyl ether methacrylate) combs synthesized in the same manner for potential effects on thermal stability in comparison to the native peptide.

AB - The controlled synthesis of poly(oligo(2-ethyl-2-oxazoline)methacrylate) (P(OEtOxMA)) polymers by Cu(0)-mediated polymerization in water/methanol mixtures is reported. Utilizing an acetal protected aldehyde initiator for the polymerization, well-defined polymers are synthesized (>99% conversion, (Eth) < 1.25) with subsequent postpolymerization deprotection resulting in α-aldehyde end group containing comb polymers. These P(OEtOxMA) are subsequently site-specifically conjugated, via reductive amination, to a dipeptide (NH2-Gly-Tyr-COOH) as a model peptide, prior to conjugation to the functional peptide oxytocin. The resulting oxytocin conjugates are evaluated in comparison to poly(oligo(ethylene glycol) methyl ether methacrylate) combs synthesized in the same manner for potential effects on thermal stability in comparison to the native peptide.

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