Tailoring Small Proteins Towards Biomedical Applications

Malgorzata      Zakrzewska; Anna      Szlachcic; Jacek      Otlewski

doi:10.2174/138920111798376905

Abstract

Over the last two decades proteins have become increasingly important in human therapy and diagnosis. Engineering therapeutic proteins through improving their biological activity and stability has been a major interest in our group. In this mini-review we summarize our research on three proteins with pharmaceutical potential – serine protease inhibitor from squash seeds (CMTI), bovine pancreatic trypsin inhibitor (BPTI), and human fibroblast growth factor 1 (FGF1). To improve the functional properties of these proteins we used multiple techniques such as homology approach, rational design, total chemical synthesis, site-directed mutagenesis and phage display. The physicochemical properties of the obtained protein variants were evaluated using protein crystallography, spectroscopic techniques, enzymatic assays, stability measurements as well as numerous biological tests.

Keywords: Protein engineering, protein therapeutics, protease inhibitors, squash inhibitors, BPTI, FGF1, protein stability, human therapy and diagnosis, homology approach, numerous biological tests, Hageman factor, pharmacological properties, antimicrobial peptides, heparan sulfate proteoglycans (HSPGs), heparans (HS)