Protein-based materials chemical synthesis

The initial preparation of protein-based polymers utilized solution and solid phase peptide chemistry. This made possible the preparation of more than 1,000 polymer compositions. As discussed in Chapter 5, these compositions were studied for determination of their basic properties, for the development of the set of phenomenological axioms for protein engineering and function, and for the demonstration of the basic mechanism that underlies function. In short, it is the chemical synthesis that has allowed development of much of the basic science and the demonstration of the potential of protein-based materials in a timely manner. Mostly because of the historical relevance, but also because of the unique contributions of chemical synthesis to arriving at satisfactory purification of microbially prepared protein-based polymers, a brief description of the chemical synthesis of protein-based polymers is given below. 

McGrath, K. and Kaplan, D. (1997) Protein-Based Materials. In Sadat-Aalaee, D., (ed.) Chemical Synthesis of Peptides and Polypeptides, pp. 3-37. Boston Bkkhauser. 

Lastly, process synthesis is important in this field. The biologists dominate process synthesis in the recombinant DNA and protein manufacturing business. What limitations prevent chemical engineers from making contributions There are two an almost complete absence of predictive models based on fundamentals and a poor understanding of the physical and chemical properties of biological materials. These issues need to be addressed in both teaching and research. 

Non-natural amino acids can be incorporated into peptides and polypeptides via several different methodologies. Solid-phase peptide synthesis (SPPS) is a straightforward method for incorporation of non-natural amino acids and allows the incorporation of essentially any amino acid but is limited by the size of the peptides produced 18). Suppression-based strategies, both in vitro and in vivo, have been developed for site specific incorporation of diverse set non-natural amino acids into natural and synthetic polypeptides 19). Alternatively, auxotrophic expression hosts have been used for multisite incorporation of nonnatural amino acid in protein polymers, where multiple natural amino acids of one type can be replaced with non-natural analogues during protein biosynthesis (20, 21). Multisite incorporation of non-natural amino acids in the synthesis of protein polymeric materials facilitates chemical modification at multiple sites and can modulate the physical properties of the protein polymers (22). 

As introduced in Chapter 1, the present chapter constitutes Assertion 4 The Applications Assertion of the book. Production and purification are first addressed, as they obviously make up the initial enabling steps in moving toward applications of any materials. The most surefooted path toward materials applications of protein-based polymers, however, intertwines issues of production and purification through a combination of the two methods of preparation—chemical synthesis and biosynthesis. Chemical synthesis proved the biocompatibility of elastic protein-based polymers and therefore opened the door to medical applications. Demonstration of the biocompatibility of the chemically synthesized product made clear the purification required of elastic protein-based polymers produced by E. coli if unlimited medical applications were to be possible. Chemical synthesis also provided a faster route to diverse polymer compositions, which allowed... 

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