A new approach to bioconjugates for proteins and peptides ("pegylation") utilising living radical polymerisation.

The synthesis of protein-polymer bioconjugates is reported using N-succinimidyl ester functionalised polymers from transition metal mediated living radical polymerisation.

Diblock copolymer micellar nanoparticles decorated with annexin-A5 proteins.

The formation of protein-decorated nanosized polymeric particles is described. Annexin-A5 protein binding to micellar aggregates having poly((1-ethoxycarbonyl)vinylphosphonic diacid) (PECVPD) and poly(n-butyl acrylate) (PBuA) as corona- and core-forming segments, respectively, was evidenced by Static and Dynamic Light Scattering (SDLS), cryo-Transmission Electron Microscopy (cryo-TEM), and Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) experiments. These new objects find potential applications, for example, in micelle-mediated target drug delivery and controlled fabrication of biochips.

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.

Alpha-aldehyde terminally functional methacrylic polymers from living radical polymerization: application in protein conjugation "pegylation".

Application of proteins and peptides as human therapeutics is expanding rapidly as drug discovery becomes more prevalent. Conjugation of polymers to proteins can circumvent many problems and pegylation of proteins is now emerging as acceptable practice. This paper describes the synthesis of alpha-aldehyde-terminated poly(methoxyPEG)methacrylates from Cu(I) mediated living radical polymerization (Mn = 11 000, 22 000 and 32 000; PDi < 1.15), and their efficient conjugation to lysozyme, as a model protein. This offers an attractive and flexible alternative to linear poly(ethylene glycol) opening up the possibility of using the full power of living radical polymerization.