Utilization of protein charge ladders in the study of protein binding orientation changes in ion-exchange chromatography

ANYL 177

Wai Keen Chung, chungw@rpi.edu, James J. Keba, pensfan200@aol.com, and Steve M. Cramer, crames@rpi.edu. Chemical and Biological Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180
Protein charge ladders were employed to carry out fundamental studies of protein binding affinity in ion exchange systems. Lysozyme charge ladders were formed through acylation of lysine residues on the protein surface with acetic anhydride. The resulting heterogeneous mixtures were evaluated with various combinations of capillary electrophoresis, ion exchange chromatography and mass spectrometry to elucidate the role of surface charge distribution and protein binding orientation on affinity in ion exchange systems. High resolution gradient ion exchange chromatography was employed to separate the complex mixture into discrete peaks that correspond to different possible combinations of acetic anhydride binding onto lysine residues. Effluent fractions were collected and subsequently analyzed using capillary electrophoresis followed by MALDI-TOF MS. In addition, tryptic digest followed by mass spec analysis was employed for specific fractions. This approach provides significant insight into what acetic anhydride binding combinations lead to changes in the binding orientation and affinity of these proteins in ion exchange systems. The implications for these findings for other complex protein mixtures is also discussed.
 

General Papers
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Analytical Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006