Journal article

Hydrolyzable Poly[Poly(Ethylene Glycol) Methyl Ether Acrylate]-Colistin Prodrugs through Copper-Mediated Photoinduced Living Radical Polymerization

Chongyu Zhu, Elena K Schneider, Vasiliki Nikolaou, Tobias Klein, Jian Li, Thomas P Davis, Michael R Whittaker, Paul Wilson, Kristian Kempe, Tony Velkov, David M Haddleton

BIOCONJUGATE CHEMISTRY | AMER CHEMICAL SOC | Published : 2017

Abstract

Through the recently developed copper-mediated photoinduced living radical polymerization (CP-LRP), a novel and well-defined polymeric prodrug of the antimicrobial lipopeptide colistin has been developed. A colistin initiator (Boc5-col-Br2) was synthesized through the modification of colistin on both of its threonine residues using a cleavable initiator linker, 2-(2-bromo-2-methylpropanoyloxy) acetic acid (BMPAA), and used for the polymerization of acrylates via CP-LRP. Polymerization proceeds from both sites of the colistin initiator, and through the polymerization of poly(ethylene glycol) methyl ether acrylate (PEGA480), three water-soluble polymer-colistin conjugates (col-PPEGA, having de..

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Grants

Awarded by EPSRC DTA award


Awarded by Leverhulme Trust


Awarded by NHMRC-ARC Dementia Research Development Fellowship


Awarded by Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology


Awarded by National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health


Awarded by Engineering and Physical Sciences Research Council


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

C.Z. was funded by an EPSRC DTA award (no. 1367109). P.W. acknowledges the Leverhulme Trust for an Early Career Fellowship (ECF/2015-075). K.K. thanks the award of an NHMRC-ARC Dementia Research Development Fellowship (no. APP1109945). The authors gratefully acknowledge the financial support from the Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology (project no. CE140100036). J.L and T.V. are supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (R01 AI111965). J.L. is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow, and T.V. is an Australian NHMRC Industry Career Development Level 2 Research Fellow. E.I.S. is an appointed Young Ambassador for the American Society of Microbiology (ASM US) and acknowledges support from the Australian Postgraduate Award.