Design and Synthesis of N-Maleimido-Functionalized Hydrophilic Polymers via Copper-Mediated Living Radical Polymerization:  A Suitable Alternative to PEGylation Chemistry

Abstract

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.

Design andIn VivoCharacterization of Immunoconjugates Targeting HIV gp160

“…The results showed that conjugation ratios of 10:1 did not decrease the specific cytotoxic activity of the IT and that the development of an anti-IT Ab response in mice was partly suppressed by PEG conjugation, despite incomplete PEGylation. These results are consistent with the effects of PEGylation on other therapeutic proteins (32)(33)(34). Other approaches to limit immunogenicity have also been proposed (35)(36)(37)(38)(39)(40).…”

Chemotactic synthetic vesicles: design and applications in blood brain barrier crossing

“…Finally, the copolymer molecular weight was checked by nuclear magnetic resonance (NMR) analysis. P(OEG 10 MA) 20 -PDPA 100 copolymer synthesis The protected maleimide initiator (Mal-Br) was prepared according to a previously published procedure (51). In a typical procedure, either ME-Br or Mal-Br initiators or ATRP initiators (0.105 mmol, 1 equiv.)…”

Design of Oligo(ethylene glycol)-Based Thermoresponsive Polymers: an Optimization Study

“…Indeed, these polymers may be synthesized using straightforward controlled radical polymerization techniques such as atom transfer radical polymerization (ATRP) [36,37] or reversible addition-fragmentation transfer polymerization (RAFT) [38][39][40], but also functionalized using versatile ligation tools such as click chemistry [41][42][43][44]. Thus, they can be easily connected to a wide variety of materials, including planar inorganic substrates (e.g., gold or glass surfaces) [45][46][47], solid or soft-matter nanoparticles (e.g., micelles, vesicles) [48][49][50][51][52] or biological structures (e.g., proteins) [53][54][55][56][57][58]. Moreover, their thermoresponsive properties can be precisely adjusted in a near-physiological range.…”