Peptide synthetic polymers, hybridization

Vandermeulen, G.W.M., and Klok, H.-A. "Peptide/protein hybrid materials enhanced control of structure and improved performance through conjugation of biological and synthetic polymers". Macromol. Biosci. 4(4), 383-398 (2004). 

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-... 

The combination of sohd phase peptide synthesis with polymer chemistry has proven to be a versatile method for the preparation of polymer-peptide hybrids. Introduction of native ligation methods even allows the synthesis of polymer modified polypeptides and proteins via an entire organic chemistry approach. In the field of polymer chemistry—besides the advances in NCA polymerization, which will be discussed by others and is therefore not part of the scope of this review—controlled radical polymerization has been shown to be a robust technique, capable of creating well-defined biofunctional polymer architectures. Through protein engineering, methods have been estabhshed that enable the construction of tailor-made proteins, which can be functionalized with synthetic polymer chains in a highly defined manner. 

Peptide-poly(ethylene glycol) (PEG) block copolymers are ofparticiflar interest, both from a structural and a functional point of view. Poly(ethylene glycol) is also often referred to as poly(ethylene oxide) (PEG). Throughout this article, however, this polyether will be referred to as PEG. In contrast to the hybrid block copolymers discussed in the previous paragraphs, which were based on amorphous synthetic polymers, PEG is a semi-crystalline polymer. In addition to microphase separation and the tendency of the peptide blocks towards aggregation, crystallization of PEG introduces an additional factor that can influence the structure formation of these hybrid block copolymers, furthermore, PEG is an FDA approved biocompatible polymer, which makes peptide-PEG hybrid block copolymers potentially interesting materials for biomedical applications. 

Over the past decade or so, these remarkable achievements by nature have been recognized by the polymer science community. This has led to an increased interest in the use of biological concepts to synthesize polymers or to control the structure and properties of synthetic polymers. Of particular interest are peptide hybrid polymers. Combining peptide and synthetic polymer segments into a single macromolecule offers interesting possibilities to synergize the properties of the individual components and to compatibilize bio- and synthetic systems. 

Shakesheff, K., Cannizzaro, S. and Danger, R., Creating biomimetic microenvironments with synthetic polymer-peptide hybrid molecules,. Biomater. Sci. Polym. Ed., 9, 507,1998. 

Klok H-A, Lecouunandoux S (2006) Solid-state structure, organization and properties of peptide-synthetic hybrid block copolymers. Adv Polym Sci 202 75-111... 

This chapter will introduce polymer systems containing either naturally occurring maaomolecules (polysaccharides, proteins, DNA) or their subunits (bioanalogous molecules, amino acids, short peptides and peptide derivatives, polypeptides, polynucleotides), respectively. The natural building blocks can be connected by covalent bonds or by self-assembly and either can be used alone (see, e.g.. Section 5.4) or in combination with synthetic polymer units (biohybrids). Alternatively the building block itself may be a hybrid of a natural and synthetic molecule (bioconjugate cf. Section 3.5), as, for instance, a PEG-peptide conjugate. 

Combining peptide sequences and synthetic polymers is useful not only for enhanced control over nanoscale structure formation, but also for production of biologically interactive materials. Biomimetic hybrid polymers may also produce sophisticated superstructures with new material properties. Smart materials based on polypeptides may reversibly change conformation and associated properties in response to an environmental stimulus, such as a shift in pH or temperature (Rodriguez-Hernandez et ah, 2005). Polypeptide block copolymers may also be used as model systems to study generic self-assembly processes in natural proteins. Obviously, such materials could be of significant interest for a variety of biomedical and bioanalytical applications. 

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