Prof. Alexander M Klibanov

The Klibanov group has discovered the rules that enable enzymes to vigorously act as catalysts in organic solvents containing little or no water. When placed in this unnatural milieu, enzymes acquire some remarkable novel properties, such as greatly enhanced thermostability and strikingly different specificity, including stereoselectivity. The ultimate goal is to obtain a mechanistic understanding of enzymatic catalysis in nonaqueous media. This knowledge will enable us to control predictably the behavior of enzymes by altering the solvent, rather than the protein molecule itself (as in protein engineering). Enzymes in organic solvents are also used as catalysts of synthetically interesting and challenging processes, such as asymmetric oxidoreductions.

The Klibanov group’s recent studies have resulted in a new, “non-release” strategy for rendering common materials (plastics, glass, textiles) permanently microbicidal. This strategy, involving covalent attachment of certain long, moderately hydrophobic polycations to material surfaces, has been proven to be very effective against a variety of pathogenic bacteria and fungi, both airborne and waterborne. This work continues along with a quest for creating material coatings with anti-viral and anti-sporal activities.

In order to be therapeutically useful, drugs have to be stable and bioavailable. Unfortunately, macromolecular pharmaceuticals are lacking in both respects. The aim is to elaborate the mechanism-based approaches to overcoming these obstacles. For example, recently the Klibanov group has undertaken a systematic investigation of the effect of selective chemical modifications of polyethylenimine (PEI) on its efficiency as a vector for plasmid DNA delivery into mammalian cells. As a result, PEI’s derivatives have been discovered with both far greater transfection efficiency and lower toxicity than those of the parent polymer (considered a “gold standard” in non-viral gene delivery vehicles).