Ronald Kluger

The study of organic chemistry at the interface of biochemistry provides a view of life processes in terms of the mechanisms of chemistry. Students in our research group can develop knowledge and skills in a broad variety of chemical and biochemical techniques, including organic synthesis, reaction kinetics, spectroscopy, enzymology, and protein chemistry. The objectives of our research are based on utilizing the principles of physical organic chemistry to provide a means of developing biochemical mechanisms and applications. Projects range from physical studies of the reactions of phosphates and organic reaction mechanisms of biochemical models to the design of enzyme inhibitors and reagents for protein modification.

We design and prepare molecules that will react with specific regions of proteins based on the presence of charge and nucleophiles. These site-directed reagents have led to the development of new materials which stabilize proteins and permit them to be used in the development of new materials and drugs. The acyl phosphate monoesters are electrophiles that are anionic, an unusual combination that permits them to react at highly specific sites. We prepare molecules based on examination of the structure of the target protein and then analyze the outcome in the modified protein. We have extended the work to produce proteins covalently linked by defined connections and have examined the effects of the protein-protein interactions.

We have developed methods to produce the intermediates in biochemical reactions of coenzymes. The covalent intermediates correspond in detail to similar enzymic intermediates, which we examine for comparison. The differences in reactivity at every step reveal the contribution of the protein.

We have found that lanthanide ions promote hydroxyl acylation reactions of acyl phosphate monoesters. We are developing the use of this specific combination to modify carbohydrates and nucleotides with site-specificity.