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

doi:10.1002/marc.201600534

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

Drug Delivery Disposition & Dynamics

Research output: Contribution to journal › Article › Research › peer-review

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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 language	English
Article number	1600534
Number of pages	7
Journal	Macromolecular Rapid Communications
Volume	38
Issue number	2
DOIs	https://doi.org/10.1002/marc.201600534
Publication status	Published - 1 Jan 2017

Keywords

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

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10.1002/marc.201600534

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Collins, J., Wallis, S. J., Simula, A., Whittaker, M. R., McIntosh, M. P., Wilson, P., Davis, T. P., Haddleton, D. M., & Kempe, K. (2017). Comb poly(oligo(2-ethyl-2-oxazoline)methacrylate)-peptide conjugates prepared by aqueous Cu(0)-mediated polymerization and reductive amination. Macromolecular Rapid Communications, 38(2), [1600534]. https://doi.org/10.1002/marc.201600534

Collins, Jennifer ; Wallis, Sacha J. ; Simula, Alexandre ; Whittaker, Michael R. ; McIntosh, Michelle P. ; Wilson, Paul ; Davis, Thomas P. ; Haddleton, David M. ; Kempe, Kristian. / Comb poly(oligo(2-ethyl-2-oxazoline)methacrylate)-peptide conjugates prepared by aqueous Cu(0)-mediated polymerization and reductive amination. In: Macromolecular Rapid Communications. 2017 ; Vol. 38, No. 2.

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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",

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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 journal › Article › Research › peer-review

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AU - Whittaker, Michael R.

AU - McIntosh, Michelle P.

AU - Wilson, Paul

AU - Davis, Thomas P.

AU - Haddleton, David M.

AU - Kempe, Kristian

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

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Keywords

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Novel targeted degradable multifunctional poly(vinyl-co-ester) nanoparticles for Alzheimer's disease applications

Macromolecular design for bio-imaging and targeted delivery

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology

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

Abstract

Keywords

Access to Document

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Novel targeted degradable multifunctional poly(vinyl-co-ester) nanoparticles for Alzheimer's disease applications

Macromolecular design for bio-imaging and targeted delivery

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology

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