AABRE: NETWORKING IN PUERTO RICO
PR-AABRE Researcher: Gabriel Barletta, Ph.D., Department of Chemistry, UPR, Humacao Campus
AABRE Cluster: Drug Design and Delivery
Collaborators: Frank Jordan, Ph.D. (Rutgers University); Marc Legault, Ph.D. (UPR, Bayamón Campus); Gustavo López, Ph.D.(UPR Mayagüez Campus); Francesco Segundo, Ph.D. (CNR-Instituto di Chimica del Riconoscimiento Moledcolare); Edmund Magner, Ph.D.(University of Limerick); Peter Halling, Ph.D. (University of Strathclyde)
Mentor: Kai Griebenow, Ph.D. (UPR, Río Piedras Campus)
Title of AABRE Project: Study of the Underlying Factors that Shape Enzyme Properties in Organic Solvents
ALL PLANT AND ANIMAL CELLS manufacture enzymes. These protein molecules function as catalysts, meaning that they make chemical reactions speed up—sometimes by a factor of many thousand times—but they are not changed by the reaction. Enzymes first came to the attention of biochemists in the 1930s, when about 80 were identified; today more than 5,000 are known.
“In addition to being very efficient catalysts, enzymes are exceptionally regio–and enantioselective; they can discriminate between molecules differing only in the orientation in space of some of their groups or atoms. Therefore, they can aid in the synthesis of a variety of new compounds which would be virtually impossible to synthesize using conventional methods,” says chemist Gabriel Barletta. Barletta and his team of researchers have begun their PR-AABRE project by studying the mechanism of enzyme catalysis in organic solvents, investigating how various solvents affect an enzyme’s activity, selectivity, and stability.
“Our goal in this project is to be able to understand how some of these enzymes work, so that they can be used towards the synthesis of compounds which are of biological relevance. Ultimately we would like to enhance the potential of enzymes for the organic synthesis of new drugs.”
Protein pharmaceuticals are often encapsulated in polymers or other matrices because they need to be protected from harsh environments. One of the first steps in this procedure is to suspend these proteins or enzymes in organic solvents to study their stability.
The researchers observe how organic solvents affect some of the properties of a model enzyme by focusing on flexibility, stability, and mechanism of catalysis. Flexibility is studied by NMR (nuclear magnetic resonance), fluorescence anisotropy decay, and electron paramagnetic resonance (EPR). Stability is observed by calorimetric and activity measurements after long-term exposure to organic solvents. A variety of kinetic methods are used to help understand the mechanism of catalysis.
“Our study will indirectly help in the search for cures of diseases by facilitating the synthesis of new chiral drugs. Chirality is a term used for molecules which are mirror images of each other. For example, your hands are chiral—one is the non-superimposable mirror image of the other.
“The receptors in our body are chiral molecules themselves, and therefore they can discriminate between other chiral molecules. Most common pharmaceuticals have chiral centers, which mean that they have one or more atoms oriented differently in space. Usually, only one of these compounds (called an enantiomer) is responsible for the desired effect of a drug. The other one is generally associated with the side effects. Since this realization, there has been an increased need, especially in pharmaceutical companies, for efficient methods and catalysts to synthesize optically pure compounds, which can be achieved through chiral synthesis.”
barletta@quimica.uprh.edu
