| Genetically directed synthesis has emerged as a powerful tool for material scientists to design and construct novel biomaterials through incorporation of sequence modules responsible for the unique structure and property of the prototype proteins. This template-driven methodology offers near absolute control on material architecture parameters such as molecular size, composition, sequence, topology, and stereochemistry which is unobtainable through conventional polymerization.; The work described herein is a result of progressive efforts of capture, analysis, and utilization of unique properties of natural proteins. Part I describes the biosynthesis and characterization of a novel polypeptide modeled on the pentapeptide sequence (Gly-Pro-Gly-Gly-Xaa) of the most resilient spider silk, flagelliform silk, with the hope to develop a new elastic material and to elucidate the elastic mechanism of flagelliform silk on molecular level. The flagelliform silk analogue was detected by a variety spectroscopic techniques to possess small but detectable population of β-turn conformers between Gly1 and Gly4 of the pentapeptide units in aqueous solution, but an increased β-turn population in the solid, low-hydrated state. The spectroscopic information suggests that the pentapeptide segments of the flagelliform silk protein adopt a β-turn conformation in the fiber, and that the mechanism of elasticity may resemble that proposed for other β-turn forming polypeptides including elastin.; Part II describes the design and characterization of a novel amphiphilic block copolymer for drug encapsulation. The lipophilic and hydrophilic blocks were derived from pentapeptide sequence of elastin (Val/Ile-Pro-Gly-Xaa-Gly) and flagelliform silk (Gly-Pro-Gly-Gly-Xaa), respectively. Morphology, structural, and fluorescence studies were undertaken to characterize the polymeric micelles and probe encapsulation capacity of the micelles in aqueous solution. Selective incorporation of elastin-mimetic polypeptide into the lipophilic block of an amphiphilic block copolymer was found to enable thermoreversible micellization and lipophilic molecule encapsulation as for conventional PEO/PPO copolymers, but allow greater variation in block sequence. The micellar morphology and polydispersity are tunable through environmental conditions such as pH and temperature. The precise control of composition, sequence, and size of block copolymer, conferred by the template-driven engineering methodology, permits rational variation of micellar structural parameters such as critical micellization temperature. |
