Synthesis and Self-Assembly of Well-Defined Block Copolypeptides via Controlled NCA Polymerization

This article summarizes advances in the synthesis of well-defined polypeptides and block copolypeptides. Traditional methods used to polymerize α-amino acid-N-carboxyanhydrides (NCAs) are described, and limitations in the utility of these systems for the preparation of polypeptides are discussed. Improved initiators and methods that allow polypeptide synthesis with good control over chain length, chain length distribution, and chain-end functionality are also discussed. Using these methods, block and random copolypeptides of controlled dimensions (including molecular weight, sequence, composition, and molecular weight distribution) can now be prepared. The ability of well-defined block copolypeptides to assemble into supramolecular copolypeptide micelles, copolypeptide vesicles, and copolypeptide hydrogels is described. Many of these assemblies have been found to possess unique properties that are derived from the amino acid building blocks and ordered conformations of the polypeptide segments. © Springer-Verlag Berlin Heidelberg 2013

Thiol chemistry on well-defined synthetic polypeptides

Well-defined cysteine-containing synthetic polypeptides were synthesised and the versatility of various chemical reactions on these thiol groups was investigated

Fluorescein functionalized random amino acid copolymers in the biomimetic synthesis of CaCO₃

In nature we find a large variety of biocomposites with complex structures to fulfill structural functions such as skeletal support and protection of soft tissues. For calcium carbonate based biominerals, acidic proteins have been reported to be instrumental in controlling the mineral formation process, including the control over nucleation, growth and polymorph selection. To unravel the crucial physicochemical characteristics of these biopolymers, we have synthesized random amino acid copolymers with varying Glu/Asp/Ala ratios using N-carboxy anhydride ring opening polymerization (NCA ROP) and a post-polymerization modification with fluorescein. As these polymers lack a specific order in their amino acid sequence, as well as a defined secondary structure under mineralization conditions, they can only influence the mineralization reactions through their amino acid composition which decides the Glu/Asp ratio and the hydrophilic/hydrophobic balance. Where P(Asp-co-Ala) produced dog-bone like crystals elongated along the crystallographic c-axis, P(Glu-co-Ala) led to the formation of rounded calcite. Also for P(Glu-co-Asp-co-Ala) the calcite crystals were elongated along the c-axis but they were overgrown with rounded calcite rhombs, crystallographically aligned with the elongated core. Hence, the ter-copolymer combines the effects of the two di-copolymers, leading to single crystals with unusual complex morphologies. The presence of a fluorescent group allowed us to study the location of the polymers in the mineral phase using fluorescence microscopy. This demonstrated that while controlling the nucleation and growth of calcite, all polymers were also incorporated within the crystals. \ua9 2011 The Royal Society of Chemistry

Selective enzymatic degradation of self-assembled particles from amphiphilic block copolymers obtained by the combination of N-carboxyanhydride and nitroxide-mediated polymerization

Combining controlled radical polymerizations and a controlled polypeptide synthetic technique, such as N-carboxyanhydride (NCA) ring-opening polymerization, enables the generation of well-defined block copolymers to be easily accessible. Here we combine NCA polymerization with the nitroxide-mediated radical polymerization of poly(n-butyl acrylate) (PBA) and polystyrene (PS), using a TIPNO and SG1-based bifunctional initiator to create a hybrid block copolymer. The polypeptide block consists of (block) copolymers of poly(l-glutamic acid) embedded with various quantities of l-alanine. The formed superstructures (vesicles and micelles) of the block copolymers possessed varying degrees of enzyme responsiveness when exposed to elastase and thermolysin, resulting in controlled enzymatic degradation dictated by the polypeptide composition. The PBA containing block copolymers possessing 50% l-alanine in the polypeptide block showed a high degradation response compared to polymers containing lower l-alanine quantities. The particles stabilized by copolypeptides with l-alanine near the hydrophobic block showed full degradation within 4 days. Particles containing polystyrene blocks revealed no appreciable degradation under the same conditions, highlighting the specificity of the system and the importance of synthetic polymer selection. However, when the degradation temperature was increased to 70 °C, degradation could be achieved due to the higher block copolymer exchange between the particle and the solution. A number of novel biohybrid structures are disclosed that show promise as enzyme-responsive materials with potential use as payload release vehicles, following their controlled degradation by specific, target, enzymes