Polymer-peptide block copolymers

Alternative total solid phase-based strategies for the preparation of polymer-peptide block copolymers were based on the polymerization of the synthetic polymer block from the supported peptide segment using either nitroxide-mediated radical polymerization (NMP) or ATRP (Fig. 15) [64,65]. 

Marsden HR, Kros A (2009) Polymer-peptide block copolymers - an overview and assessment of synthesis methods. Macromol Biosci 9 939-951... 

In this paper we describe the synthesis and the structure of 5 types of vinyl-peptide block copolymers, namely polybutadiene-poly (ybenzyl-L-glutamate) (BG), polybutadiene-poly(e-carbobenzoxy-L-lysine) (BCK), polystyrene-poly(y-benzyl-L-glutamate) (SG), polys-tyrene-poly(e-carbobenzoxy-L-lysine) (SCK) and poly(y-benzyl-L-glu-tamate)-polybutadiene-poly(y-benzyl-L-glutamate) (GBG), and the results of the hemocompatibility tests performed on some of these polymers. ... 

Habraken GJM, Koning CE, Heise A (2009) Peptide block copolymers by N-carboxyanhydride ring-opening polymerization and atom transfer radical polymerization the effect of amide macroinitiators. J Polym Sci A Polym Chem 47 6883-6893... 

The synthesis of some multiblock copolymers was attempted by successive polymerization using this iniferter technique. However, pure tri- or tetrablock copolymers free from homopolymers were not isolated by solvent extraction because no suitable solvent was found for the separation. In 1963, Merrifield reported a brilliant solid-phase peptide synthesis using a reagent attached to the polymer support. If a similar idea can be applied to the iniferter technique, pure block copolymer could be synthesized by radical polymerization. The DC group attached to a polystyrene gel (PSG) through a hydrolyzable ester spacer was prepared and used as a PSG photoiniferter (Eq. 53) [186] ... 

Investigations on a block-copolymer of PEG and polystyrene also showed that in the solid state, the amorphous polystyrene occupies a space between two PEG blocks 179). These observations suggested a similar two-phase model for the PEG-peptides in the solid state which explains the high retention of crystallinity of the polymer even when it is bound to amorphous peptides 180). 

Linear polystyrene can be functionalized by various methods . The functional group capacity in these polymers diould not be too high otherwise, steric complications may arise. Poly(ethylene ycol) has been found to be most suitable for liquid-phase synthesis. This linear polyether and the block copolymers with functional groups at defined distances are chemically stable and soluble in a large number of solvents including water and can be precipitated selectively. Partially hydrolyzed poly(vinylpyrrolidone) and its copolymers with vinyl acetate were successfully applied in peptide synthesis. Poly(acrylic acid), poly(vinyl alcdiol), and poly-(ethylenimine) are less suitable for the sequential type synthesis because of the... 

Synthetic peptide-based polymers are not new materials homopolymers of polypeptides have been available for many decades and have only seen hmited use as structural materials [5,6]. However, new methods in chemical synthesis have made possible the preparation of increasingly complex polypeptide sequences of controlled molecular weight that display properties far superior to ill-defined homopolypeptides [7]. Furthermore, hybrid copolymers, that combine polypeptide and conventional synthetic polymers, have been prepared and combine the functionality and structure of peptides with the processabihty and economy of polymers [8,9]. These polymers are well suited for applications where polymer assembly and functional domains need to be at length scales ranging from nanometers to microns. These block copolymers are homogeneous on a macroscopic scale, but dissimilarity between the block segments typically results in microphase heterogeneity yield-... 

In this review the different synthetic strategies for constructing polymer-peptide hybrids will be discussed, as well as some of the characteristic features of the materials. The complexity of the hybrid structures prepared will increase as this review progresses, starting with the controlled polymerization of peptide-containing monomers and later covering the creation of block copolymer structures via a protein engineering approach. 

For both designs a microphase separated morphology was found with 20-50 nm peptide domains dispersed in a continuous poly(ethylene glycol) phase. Furthermore, a 100-150 nm superstructure was observed in cast films, which was explained to result from the polydispersity and multiblock character of the polymers. The mechanical properties of fibers and films made from these block copolymers could be modulated by manipulating the length and nature of the constituent blocks. Similar work was reported by Shao et al. [47]. 

Becker et al. [64] functionalized a peptide, based on the protein transduction domain of the HIV protein TAT-1, with an NMP initiator while on the resin. They then used this to polymerize f-butyl acrylate, followed by methyl acrylate, to create a peptide-functionahzed block copolymer. Traditional characterization of this triblock copolymer by gel permeation chromatography and MALDI-TOF mass spectroscopy was, however, comphcated partly due to solubility problems. Therefore, characterization of this block copolymer was mainly hmited to ll and F NMR and no conclusive evidence on molecular weight distribution and homopolymer contaminants was obtained. Difficulties in control over polymer properties are to be expected, since polymerization off a microgel particle leads to a high concentration of reactive chains and a diffusion-limited access of the deactivator species. The traditional level of control of nitroxide-mediated radical polymerization, or any other type of controlled radical polymerization, will therefore not be straightforward to achieve. 

---