Dr. Richard DiMarchi
Indiana University

"The Emergence of Chemical Biotechnology
as a Means to Optimal Protein-Based Medicines"

ABSTRACT

The recent emergence of new technologies in protein biosynthesis is dramatically enlarging the structural space that can be utilized by protein medicinal chemists. The simultaneous mutation of tRNAs and the tRNA-Synthetases has demonstrated that amino acids previously restricted to chemical synthetic approaches can now be successfully utilized in rDNA-based biosynthesis. Additionally, advances in fragment ligation peptide chemistries have proven that proteins of appreciable synthetic complexity can be readily prepared in quantity and quality sufficient to support a structure activity relationship. This period in protein chemistry is quite analogous to the advent of rDNA-based synthesis when the first natural sequenced proteins were produced and the foundation for the delivery of optimized proteins was established. The structure-activity relationships that delivered those first commercial hormone analogs, such as LisPro-human insulin were conducted by a combination of synthetic, semi-synthetic and biosynthetic methodologies. The integration of these new synthetic tools with more conventional methodologies is dramatically enhancing the academic and commercial opportunities in protein chemistry.