Copolymers, copolypeptide

Besides the polypeptide hybrid block copolymers described earlier, there exist a few examples of purely peptide-based amphiphiles and block/random copolymers (copolypeptides) (Fig. 10). In the latter case, both the core and corona of aggregates consist of a polypeptide. Any of the studies reported so far dealt with aggregation in aqueous media. 

In 2000, the first example of ELP diblock copolymers for reversible stimulus-responsive self-assembly of nanoparticles was reported and their potential use in controlled delivery and release was suggested [87]. Later, these type of diblock copolypeptides were also covalently crossUnked through disulfide bond formation after self-assembly into micellar nanoparticles. In addition, the encapsulation of l-anilinonaphthalene-8-sulfonic acid, a hydrophobic fluorescent dye that fluoresces in hydrophobic enviromnent, was used to investigate the capacity of the micelle for hydrophobic drugs [88]. Fujita et al. replaced the hydrophilic ELP block by a polyaspartic acid chain (D ). They created a set of block copolymers with varying... 

ELP-based triblock copolypeptides have also been used to produce stimulus-responsive micelles, and Chaikof and coworkers envisioned the possible application of these micelles as controlled drug delivery vehicles. These amphiphilic triblock copolymers were constructed from two identical hydrophobic ELP endblocks and a hydrophilic ELP midblock. Below the transition temperature, loose and monodispersed micelles were formed that reversibly contracted upon heating, leading to more compact micelles with a reduced size [90]. 

Fig. 1 Vesicle construct formed from poly(L-lysine)-i)-poly(L-leucme) polypeptides where the poly(L-leucine) block corresponds to the a-helical hydrophobic segments and the poly (L-lysine) block corresponds to the random coil hydrophilic segments. Note that this is one specific example and not all vesicle constructs have a-helical and random coil blocks. Moreover, the amphiphilic copolymer can be comprised of either a pure block copolypeptide or a macromolecule consisting of a polypeptide and another type of polymer. Adapted from [20] with permission. Copyright 2010 American Chemical Society...

Polymeric polypeptides have long been the focus of many research groups and are, therefore, covered in Section 14.2. Early on, these polymers were considered to be protein model structures. Discussions of homopolypeptides prepared by a-amino acid TV-carboxy-anhydride (NCA) polymerizations are an important part of the volume (Sections 14.2,14.2.1, and 14.2.1.1). 19,20 Copolypeptides are prepared by routes which lead to random or sequential copolymer structures (Sections 14.2.2 and 14.2.3).[21,22 ... 

Investigations on diblock copolypeptide amphiphiles by Deming and coworkers further elegantly proved the dependence of the aggregation behavior on the chain conformation of the polymer blocks.225 Well-defined block copolymers were synthesized containing... 

Abstract The aggregation behaviour of biomimetic polypeptide hybrid copolymers and copolypeptides is here reviewed with a particular eye on the occurrence of secondary structure effects. Structure elements like a-helix or / -sheet can induce a deviation from the classical phase behaviour and promote the formation of vesicles or hierarchical superstructures with ordering in the length-scale of microns. Polypeptide copolymers are therefore considered as models to study self-assembly processes in biological systems. In addition, they offer a great potential for a production of novel advanced materials and colloids. 

This review covers the literature on the aggregation of (homo)polypeptide hybrid copolymers and copolypeptides in dilute solution, which was published up to June 2005 a recent review on amphiphiles consisting of peptide sequences is given elsewhere in [12]. It was a particular concern to give a comprehensive overview on secondary structure effects in the self-assembly of these copolymers. Briefly presented are also structures in concentrated solutions (lyotropic phases) and in heterophase systems (see also [14]). 

The linear polypeptide hybrid block copolymers and block copolypeptides reported to form vesicles in aqueous solution are listed in Fig. 1. 

Nonionic block copolypeptides made of PEGylated L-lysine and L-leucine residues, PELLys- -PLLeu (Fig. lOh) have also been described [52], The copolymers adopted a rod-like conformation, due to the strong tendency of both segments to form a-helices (CD spectroscopy), and produced a variety of self-assembled structures in aqueous solution. Micrometer vesicles and sheet-like membranes could be obtained for copolymers with fractions of the hydrophobic leucine ranging from 10 to 30mol%. Conventional uncharged block copolymers of this composition would be expected to form spherical or cylindrical micelles. The assembly into bilayers was related to a secondary structure effect, as illustrated in Fig. 12. Accordingly, samples with the same composition but nonhelical chain conformation (CD),... 

The relationship between the copolymer composition for copolypeptides has been studied. Figures 25 and 26 show the plots of the criso data of the Ala residue in [Ala, Leu] and [Ala, Val] , respectively, against the L-alanine content (%). For a series of [Ala, Leu] , where Leu has a hydro-phobic alkyl side-chain and stabilizes an a-helix conformation, criso is found to be almost constant over a wide range of L-alanine contents (5 80%). 

Analogous photoresponsive peptide and polypeptide systems are being developed the photochemical properties of poly[W -p-(phenyl-azo)benzoyl-L-a,/8-diaminopropionic acid] have been examined, and the first example of photoregulation of permeability across a membrane has been achieved by the use of a new polyvinyl/poly-peptide graft copolymer composed of a photoresponsive copolypeptide branch from /3-p-phenylazobenzyl L-asparate and /3-benzyl L-asparate attached to a poly(Bu methacrylate) backbone.Papain activity has similarly been regulated by anchoring a photo-responsive azo group to the enzyme backbone. ... 

---