Chemical and Genetic Engineering Strategies to Improve the Potency of Pharmaceutical Proteins and Enzymes

Dimitris      Platis; Nikolaos   E.   Labrou

doi:10.2174/092986708785132924

Abstract

Over the last decade there has been significant progress in understanding the molecular basis of disease processes. At the same time the technological advances in the area of genomics and the efforts in proteomics research have increased the possibility of discovering many proteins with defined therapeutic functions. A large number of these proteins have found clinical application. Despite the importance of proteins as therapeutic agents, they have a number of disadvantages in comparison to small-molecule drugs, including immunogenicity and antigenicity, poor efficacy and oral bioavailability as well as, in many cases, short serum half-lives. To date, the most promising approaches for improving protein therapeutics rely on the use of genetic engineering and site-specific chemical synthesis/ modification techniques. Improving the potency of protein drugs by employing modern recombinant DNA technologies and novel chemical synthesis techniques is of primary importance, not only because of the enormous medicinal benefit but also because of the significant economic edge an improved drug can provide in todays competitive market.

Keywords: Expressed protein ligation, chemoselective ligation, directed evolution, native ligation, PEG, PEGylation, protein and enzyme engineering, rational protein design, semisynthetic proteins