Design and synthesis of N-maleimido-functionalized hydrophilic polymers via copper-mediated living radical polymerization: a suitable alternative to PEGylation chemistry.
A series of alpha-functional maleimide polymethacrylates (M(n) = 4.1-35.4 kDa, PDi = 1.06-1.27) have been prepared via copper-catalyzed living radical polymerization (LRP). Two independent synthetic protocols have been successfully developed and the polymers obtained in multigram scale, with an 80-100% content of maleimide reactive chain ends, depending on the method employed. A method for the synthesis of amino-terminated polymers, starting from Boc-protected amino initiators, has also been developed, as these derivatives are key intermediates in one of the two processes studied in the present work. The alternative synthetic pathway involves an initiator containing a maleimide unit "protected" as a Diels-Alder adduct. After the polymerization step, the maleimide functionality has been reintroduced by retro-Diels-Alder reaction, by simply refluxing those polymers in toluene for 7 h. These maleimido-terminated materials, poly(methoxyPEG((475))) methacrylates and poly(glycerol) methacrylates, differ for both the nature and size of the polymer side branches and showed an excellent solubility in water, a property that made them an ideal candidate for the synthesis of new polymer-(poly)peptide biomaterials. These functional polymers have been successfully employed in conjugation reactions in the presence of thiol-containing model substrates, namely, reduced glutathione (gamma-Glu-Cys-Gly) and the carrier protein, bovine serum albumin (BSA), in 100 mM phosphate buffer (pH 6.8-7.4) and ambient temperature.
Mantovani
Giuseppe
G
Department of Chemistry, University of Warwick, CV4 7AL, Coventry, UK.
Lecolley
François
F
Tao
Lei
L
Haddleton
David M
DM
Clerx
Joost
J
Cornelissen
Jeroen J L M
JJ
Velonia
Kelly
K
D003300:Copper / Q000737:chemistry*; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D005978:Glutathione / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008301:Maleimides / Q000138:chemical synthesis* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry*
D004337:Drug Carriers; D008301:Maleimides; D011109:Polymethacrylic Acids; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D003300:Copper; D005978:Glutathione