Caspofungin functionalized polymethacrylates with antifungal properties.

Alex J, Gonzalez K, Kindel T, Bellstedt P, Weber C, Heinekamp T, Orasch T, Guerrero-Sanchez C, Schubert US, Brakhage AA (2020) Caspofungin functionalized polymethacrylates with antifungal properties. Biomacromolecules 21(6), 2104-2115.


We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) PmPEGMA and hydrophobic poly(methyl methacrylate) (PMMA) caspofungin conjugates by a post polymerization modification of copolymers containing 10 mol% pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition fragmentation chain transfer copolymerization. The coupling of the clinically used antifungal caspofungin was confirmed and quantified in detail by combination of 1H-, 19F- and diffusion ordered nuclear magnetic resonance spectroscopy, UV-Vis spectroscopy and size exclusion chromatography. The trifunctional amine-containing antifungal was attached via several amide bonds to the hydrophobic PMMA but sterical hindrance induced by the mPEGMA side chains prohibited intramolecular double functionalization. Both polymer-drug conjugates revealed activity against important human-pathogenic fungi, i.e., two strains of Aspergillus fumigatus and one strain of Candida albicans (2.5 mg L 1 < MEC < 8 mg L-1, MIC50 = 4 mg L-1) whereas RAW 264.7 macrophages as well as HeLa cells remained unaffected at these concentrations.


Axel A. Brakhage
Katherine Gonzalez Rojas
Thorsten Heinekamp
Till Kindel
Thomas Orasch


doi: 10.1021/acs.biomac.0c00096

PMID: 32286800