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Research Focus

Biocatalysis with Antibodies and Enzymes, Organic Synthesis, Drug Discovery, Biomolecular Computing Devices

Catalytic antibodies: We study antibody catalyzed photochemical reactions, oxidation reactions and organometallic reactions. For example, while the solution photochemical reaction of an aliphatic ketone yields only the cleavage products, in the presence of antibody, 20F10, this Norrish type II reaction results in the selective formation of cis cyclobutanol. During our on-going efforts to develop catalytic antibodies for organometallic reactions we discovered new aqueous chemistry of platinum that is relevant to the transition-metal catalyzed activation of alkanes.

Novel catalytic activities with synthetic proteins: Efforts to generate new enzymatic activities from existing protein scaffolds represents a major challenge. We accomplished a profound change in the catalytic activity and mechanism of 4-oxalocrotonate tautomerase (4-OT) by a rationally designed single amino acid substitution that corresponds to a single base pair mutation. The observation that a single catalytic group in an enzyme can catalyze two reactions by two different mechanisms supports the theory that new enzymatic activity can evolve in a continuous manner.

Synthetic methodology, total synthesis, drug discovery: We have developed a single-step, tandem oxidative polycyclization reaction with rhenium(VII) reagents as a powerful methodology by which polyene alcohols can be converted into polytetrahydrofuran products in a single step. We have also developed synthetic approaches that can be used to generate chemical libraries of stereoisomeric Annonaceous acetogenins, particularly those that have exhibited remarkable antitumor activity.

Molecular computing devices: We have recently introduced the first nanoscale, programmable finite automaton that computes autonomously with all of its components, including hardware, software, input and output being biomolecules, mixed together in solution. Now we are taking the concept of molecular computing one step further and obtain computation outputs in the form of specific biological functions.

Selected References

Shulman, H., Makarov, C., Ogawa, A.K., Romesberg, F., Keinan, E. Chemically reactive immunogens lead to functional convergence of the immune response. J. Am. Chem. Soc. 122:10743, 2000.

D’Souza, L.J., Sinha, S.C., Lu, S.-F., Keinan, E., Sinha, S.C. Oxidative polycyclization with rhenium(VII) oxides. Application of the stereoselectivity rules in the total synthesis of Rollidecins C and D. Tetrahedron 57:5255, 2001.

Benenson, Y., Paz-Elizur, T., Adar, R., Keinan, E., Livneh, Z., Shapiro, E. Programmable and autonomous computing machine made of biomolecules, Nature, 414:430, 2001.

Lo, H.C., Haskel, A., Kapon, M., Keinan, E. TpPt(IV)Me(H)2 forms a s-CH4 complex that is remarkably resistant to methane liberation. J. Am. Chem. Soc. 124:3226, 2002.

Links

The Skaggs Institute Scientific Report