Protein-like copolymers

This strategy was first realized by Lozinsky et al., who studied the redox-initiated free-radical copolymerization of thermosensitive N-vinylcaprolactam with hydrophilic N-vinylimidazole at different temperatures, as well as by Chi Wu and coworkers. Lozinsky presents an extensive review of the experimental approaches, both already described in the literature and potential new ones, to chemical synthesis of protein-like copolymers capable of forming core-shell nanostructures in a solution. 

Khokhlov AR, Ivanov VA, Shusharina NP, Khalatur PG (1998) Engineering of synthetic copolymers protein-like copolymers. In Yonezawa F, Tsuji K, Kaij K, Doi M, Fujiwara T (eds) The physics of complex liquids. World Scientific, Singapore, p 155... 

Approaches to Chemical Synthesis of Protein-Like Copolymers... 

Abstract Protein-like copolymers were first predicted by computer-aided biomimetic design. These copolymers consist of comonomer units of differing hydrophilicity/hydro-phobicity. Heterogeneous blockiness, inherent in such copolymers, promotes chain folding with the formation of specific spatial packing a dense core consisting of hydrophobic units and a polar shell formed by hydrophilic units. This review discusses the approaches, those that have already been described and potential approaches to the chemical synthesis of protein-like copolymers. These approaches are based on the use of macromolecular precursors as well as the appropriate monomers. In addition, some specific physicochemical properties of protein like copolymers, especially their solution behaviour in aqueous media, are considered. 

Keywords Chemical synthesis Heterogeneous blockiness Physicochemical studies Protein-like copolymers Solution behaviour... 

After the publication of the first theoretical works related to the problem of protein-like copolymers, the first attempts to verify experimentally these theoretical concepts were undertaken. Several research groups have tried to... 

Fig. 1 Typical snapshot of a protein-like copolymer macromolecule, in which H monomeric units are shown as dark grey spheres and P units are shown as light grey spheres (adopted from [13])... 

The copolymer-based systems possessing the core-shell structure in solutions are known and studied rather well (see, e.g., [14-16]). These copolymers in aqueous media tend to form polymeric micelles, which are often considered as promising drug delivery nano-vehicles [ 17,18], i.e., these macromolecular systems are not only of scientific, but also of considerable applied significance. Among such systems there are interesting examples, whose properties are very similar to the properties that should be inherent in the protein-like copolymers. All of these macromolecules possess the primary structure of... 

In the researches performed by Tenhu and co-authors [19-21], it was shown that by means of chemical modification of the units with reactive pendant groups in thermoresponsive NiPAAm-containing copolymers one can prepare polymeric products, whose solution behaviour resemble in some aspects the behaviour predicted by the theory for protein-like copolymers. Scheme 1 presents the reaction used in these syntheses. 

In this section we will touch upon an alternative route for the synthesis of protein-like copolymers using the chemical colouring approach, i.e., the... 

A general idea related to the preparation of protein-like copolymers through the co-polymerization or co-polycondensation of the mixtures of comonomers with differing hydrophilicity/hydrophobicity has been described in Sect. 2.1. Scheme 4 demonstrates the multi-step operations used in the first successful realization [26,27] of such an approach in a free radical polymerization process. 

The transition enthalpies of the s- and p-fractions obtained from the feed with a comonomer molar ratio of 85 15 were equal to 6 and 7 J/g, respectively, i.e. the values are very close. This, therefore, can be indicative of almost the same average length of oligoNVCl blocks. Moreover, as we have already stressed, the fractions also had virtually the same final comonomer composition. However, since the solution properties of these fractions are drastically different, one can draw the conclusion that this is apparently due to a specific distribution of hydrophobic and hydrophilic residues along the polymer chains. In turn, because of all the properties that are exhibited by the s-fraction, this fraction can be considered to be a protein-like copolymer [27]. 

Generally speaking, we should note that the synthetic potentials of the polycondensation approach for the preparation of protein-like copolymers are only now beginning to be explored. Nonetheless, even the first results show promising directions for future synthetic developments that can hardly be reached through the polymerization processes. 

Another (quite different) implication of the issue of information capacity of protein-like copolymer is the possibility of recording a small region in conformation space near the native state instead of recording several essentially different conformations in the polymer sequence. Moreover, this can be done so that the transitions between the conformations within the above-mentioned region occur fast, without barriers, and possibly in an ordered... 

Lozinsky V.I. Approaches to Chemical Synthesis of Protein-Like Copolymers. Vol. 196, pp. 87-128. 

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