Dr. JANICE A. LUMPKIN  Assistant Professor (1958-1997)

S.B. 1980, Chemical Engineering, Massachusetts Institute of Technology.
M.S. 1984, Chemical Engineering, University of Pennsylvania.
Ph.D. 1988, Chemical Engineering, University of Pennsylvania

Protein Stability and Modeling of Oxidative Reactions. The successful use of proteins in therapeutic, industrial, and food-related applications has been impeded by stability problems. Metal ion-catalyzed oxidation (MCO) of proteins is a largely unexplored class of reactions which recently have been recognized to inactivate or degrade several therapeutic and industrial proteins. MCO reactions require O2, transition metals and reductants commonly found in bioprocessing. These reactions typically proceed via radical chain reactions involving active oxygen intermediates such as hydroxyl radicals (·OH). In order to assess the magnitude of this stability problem and make effective process design and/or protein engineering decisions, quantitative kinetic models of MCO reactions must be developed and highly reactive peptide sequences must be identified.

Recently we have shown that MCO reactions occur during immobilized metal affinity chromatography (IMAC) under industrially relevant conditions. We have also shown that the complex concentration dependencies of these reactions can be predicted with kinetic simulation models. Current research activities are focused on experimental measurement and mathematical modeling of rates of ·OH formation, loss of enzymatic activity and peptide damage in MCO solutions containing chelators and IMAC columns. Metal and metal-chelate binding to proteins and peptides is also under investigation.

Delivery of Protein Pharmaceuticals. Most protein pharmaceuticals are extremely fragile molecules which must be administered to patients by repeated injections. This can lead to patient compliance problems and diminished quality of life. One solution to this problem is delivery of these medications by controlled release from biodegradable microcapsules. We are investigation the effect of the microencapsulation process on protein stability. Thermodynamic, structural and kinetic analyses are being conducted for each processing step which includes micelle formation and lyophilization (freeze drying).

Madurawe, R. D., and Janice Lumpkin, Quantitation of protein damage in metal ion-catalyzed oxidation systems, Chem. Eng. Comm., (in press).

Madurawe, R. D., Lin, Z., Dyden, P., and Lumpkin, Janice, Stability of lactate dehydrogenase in metal catalyzed oxidation solutions containing chelated metals, Biotech. Prog., 13, 179-184 (1997).

Lumpkin, J.A., D.D. Perlmutter, Thermal and Water Vapor Effects on the Rate of the Dehydration Reactions of Hydrated Barium Chloride, Therm. Acta, 249, 335-349 (1995).

Krishnamurthy, R., R. D. Madurawe, K. D. Bush and J. A. Lumpkin, Conditions Promoting Metal Catalyzed Oxidation During Immobilized Cu - Iminodiacetic Acid Metal Affinity Chromatography, Biotech. Progress, 11, 643-650 (1995).

Lumpkin, J.A., D.D. Perlmutter, Diffusional Limitations on the Kinetics of Dehydration Reactions of Hydrated Barium Chloride, Therm. Acta, 249, 335-349 (1995).

Singh, M., J.A. Lumpkin, J. Rosenblatt, Effect of Electrostatic Interactions on Polylysine Release Rates from Collagen Matrices and Comparison with the Model Predictions, J. of Control. Rel., 35, 165-179 (1995).

Singh, M., J.A. Lumpkin, J. Rosenblatt, Mathematical Modeling of Drug Release from Hydrogel Matrices via a Diffusion Coupled with Desorption Mechanism, J. Control. Rel., 32, 17-25 (1994).