stage further by complementarity-determining region (CDR) grafting, where the 34 CDRs of mouse antibodies were grafted onto human frameworks to reduce the proportion of mouse sequences in the drug still further while retaining binding specificity [115].
2.3.3.3.1 Insulin
Insulin was engineered through mutagenesis to create monomeric forms that are fast acting (insulin lispro and insulin aspart). Conversely, another form (insulin glargine) was created by mutagenesis to precipitate upon injection and give a sustained release of insulin. More research was done on insulin. Whittingham et al. 1997 reported a crystal structure of a prolonged-acting insulin with albumin-binding properties [116].
2.3.3.3.2 Catalytic Antibody
A catalytic antibody is a variant of an antibody. Antibodies are proteins that normally bind to a specific molecule but do not alter the bound molecule in any way. A catalytic antibody is one which was changed by mutations to have a novel sequence that folds into a structure that catalyzes a specific reaction (such as amide bond formation, ester hydrolysis, and decarboxylation). Catalytic antibodies function like enzymes, and are created to catalyze reactions for which there are no naturally occurring enzymes. Fifty or more different reactions have been catalyzed by the action of catalytic antibodies that were obtained individually by methods of protein engineering [117].
2.3.3.3.3 Polyketide Synthases
Antibiotics such as erythromycin are made by large multidomain proteins called polyketide synthases. Site-directed mutagenesis was used to modify the substrate specificity of one polyketide synthase reaction so that the product contains a malonate unit, whereas the product of the original enzyme contained a methylmalonate unit. In addition to site-directed mutagenesis, the order of the polyketide synthase domains was shuffled to create proteins that could catalyze the synthesis of new antibiotics. An extension of site-directed mutagenesis allows non-natural amino acids to be incorporated into proteins. Non-natural amino acids are not naturally encoded by the genome, but instead include a wide variety of amino acids that are present in cells or produced by synthetic methods [117].
2.3.4 Traditional Protein
2.3.4.1 Casein
Casein is a natural polymer extracted from skimmed milk proteins. Casein protein is used in many industrial and technical applications [71, 118, 119], such the manufacture of adhesives and the packaging industry for breweries, wineries and refrigerated products and it can also be used as a plasticizer for concrete. Casein is also used as microcapsules and in synthetic peptides [120]. Caseins evolved from members of a group of secreted calcium (phosphate)-binding phosphoproteins. The first industrial applications of protein as polymer were in the early 1930s and 1940s with casein and with soy protein. Casein is also used as microcapsules and in synthetic peptides [75, 121].
2.3.4.2 Keratin
Keratin derived materials have shown potential to transform the world of bio-based materials because of their intrinsic biocompatibility, biodegradability, mechanical durability, and natural abundance [58]. keratin is the most abundant structural protein in epithelial cells [122] and a most important biopolymer in animals along with collagen. Keratin is a polypeptide consisting of amino acids having intermolecular bonding of cysteine and few intramolecular bonding of polar and non-polar groups. The cysteine residues have thiol groups which produce strong disulfide bonds leading to the cross-linking of the matrix molecule. Keratins can be exited as delicate keratins (such as stratum corneum) generally poorly united and with a lower measure of sulfur and lipids, and hard keratins found in hair [123], nails, paws, noses, feathers [124], plumes, which have a more rational structure and a higher measure of sulfur.
2.3.4.3 Worm and Spider Silk
Silk is a polymer made from the fine threads produced by certain insect larvae. Silk was traditionally known to be produced from the silk worm [125]. Silk is, by nature, a protein biopolymer produced by polymer producer organisms. Examples of silk producers are spiders, silkworms [126], mites [127], scorpions and flies [128]. There is a rise in interest in the silk produced by spiders [129]. Spider silk is an interesting biomaterial, elastic and strong that is comparable to the best fibers synthetized by new technology in terms of mechanical properties. It is also a biodegradable material and environmentally safe. Because of the limited amount of spider silk, silk fibroin as a natural polymer produced by silkworms is a good alternative. Sericin and fibroin are the major components of it. Fibroin, a fibrous protein creating the silk core, is composed of a fibroin light chain, fibroin heavy chain and fibrohexamerin. Excellent mechanical properties, biocompatibility and slow degradability make this material interesting.
2.3.4.4 Collagen, Gelatin, Elastin, Albumine and Fibrin
Collagen and gelatine are animal polymers found in skin and connective tissues. Collagen degraded to high molecular weight polypeptide, called gelatine, can be obtained by thermal denaturing of collagen. Gelatin is a water-soluble proteinaceous substance [130]. Gelatin is an important high molecular weight polypeptide hydrocolloid. It is commonly used in a wide range of food, medicinal, pharmaceutical, and polymeric materials. Most hydrocolloids are polysaccharide, whereas gelatin is a protein containing all the amino acids except tryptophan [131]. It was fabricated to different forms to match different applications [132]. It is essential in drug caps, X-rays, photographic film development and food processing. Gelatin grades used in drug delivery and tissue engineering are also available in a wide range of viscosities. It does not show antigenity and is resorbable in vivo. Its physico-chemical properties can be suitably modulated. Gelatine can be plasticized thanks to the addition of water or of glycerol. There is, however, a limit to the use of this interesting material because there is a risk of viral animal contamination. Blends of polyvinyl alcohol and gelatine are the object of studies and research. Elastin, albumine and fibrin are other proteins from animal sources. They have been investigated especially for various biomedical applications. Elastin is used as a biopolymer in enhancing cellular uptake in the tumor cells [82, 83, 133–136].
2.3.4.5 Wheat Gluten
Wheat gluten is a protein by-product of the starch fabrication. In addition to wheat, grain sources of gluten are barley, rye, triticale, spelt, einkorn, emmer and kumut. It is available in high quantity and at low cost [137]. Gluten is a part of our food and is contained in pasta, bread, cereals, soups, deserts, soy sauce, hydrolyzed wheat proteins, wheat bran hydro lysate, wheat protein isolate, wheat starch, glucose syrups, wheat maltodextrin, sorbitol, lactitol, maltitol, caramel, glucan, alcohol/ ethanol, vinegar, wheat germ oil, medications, and so on. They are relatively impermeable to oxygen and to CO2 but are sensitive to humidity. Potential applications are producing soluble receptacles for the controlled release of a chemical product (such as toilet detergent). Wheat gluten contains two main groups of proteins, gliadin and glutenin [138]. Gliadins are protein molecules with disulphide bonds. They have low molecular weight and a low level of amino acids with charged side groups. Gliadin has antimicrobial activity and is used in food packaging and coating applications [130, 139].
The molecular weight of glutenins is at least ten times higher than that of gliadins. Wheat gluten materials have the fastest degradation rates. Gluten is fully biodegradable and the products obtained are non-toxic. Wheat gluten has proved to be an excellent film-forming agent [18, 140]. In practice, the term “gluten” refers to the proteins, because they play a key role in determining the unique baking quality of wheat by conferring water absorption capacity, cohesivity, viscosity and elasticity to dough. It is also used for improving solubility, emulsification, and film-forming properties [22, 141, 142]. The amino acid compositions of glutenins are similar to those of gliadins, with high levels of glutamine and proline and low levels of charged amino acids. Glutenins can be broadly classified into two groups, the high molecular weight (HMW) and the low molecular weight (LMW) subunits.