Abstract

The central focus of this research will be the use of affinity capillary electrophoresis (ACE), in combination with charge ladders derived from proteins, to investigate electrostatic interactions important in protein biochemistry: acidities of functional groups, interactions among charged groups on proteins, electrostatic contributions to binding of ligands to proteins, and screening of electrostatic interactions involving proteins by ions in solution. These studies will be extended by detailed experimental studies of small, non-protein biomolecules (vancomycin and its derivatives, cyclodextrins and their derivatives, substrates such as ATP, cofactors such as NAD(P)(H), oligonucleotides), and by theoretical analyses based on the Poisson-Boltzmann equation. The research will also apply ACE to problems in biomolecular recognition that do not explicitly involve electrostatic interactions: polyvalency will be the most important of these problems.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM051559-05
Application #
2771010
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1994-09-02
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

Shaw, Bryan F; Schneider, Gregory F; Whitesides, George M (2012) Effect of surfactant hydrophobicity on the pathway for unfolding of ubiquitin. J Am Chem Soc 134:18739-45
Shaw, Bryan F; Schneider, Gregory F; Arthanari, Haribabu et al. (2011) Complexes of native ubiquitin and dodecyl sulfate illustrate the nature of hydrophobic and electrostatic interactions in the binding of proteins and surfactants. J Am Chem Soc 133:17681-95
Lee, Andrew; Mirica, Katherine A; Whitesides, George M (2011) Influence of fluorocarbon and hydrocarbon acyl groups at the surface of bovine carbonic anhydrase II on the kinetics of denaturation by sodium dodecyl sulfate. J Phys Chem B 115:1199-210
Lee, Andrew; Tang, Sindy K Y; Mace, Charles R et al. (2011) Denaturation of proteins by SDS and tetraalkylammonium dodecyl sulfates. Langmuir 27:11560-74
Mecinovic, Jasmin; Snyder, Phillip W; Mirica, Katherine A et al. (2011) Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the ""hydrophobic wall"" of carbonic anhydrase. J Am Chem Soc 133:14017-26
Snyder, Phillip W; Mecinovic, Jasmin; Moustakas, Demetri T et al. (2011) Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase. Proc Natl Acad Sci U S A 108:17889-94
Lee, Andrew; Whitesides, George M (2010) Analysis of inorganic polyphosphates by capillary gel electrophoresis. Anal Chem 82:6838-46
Shaw, Bryan F; Arthanari, Haribabu; Narovlyansky, Max et al. (2010) Neutralizing positive charges at the surface of a protein lowers its rate of amide hydrogen exchange without altering its structure or increasing its thermostability. J Am Chem Soc 132:17411-25
Krishnamurthy, Vijay M; Kaufman, George K; Urbach, Adam R et al. (2008) Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. Chem Rev 108:946-1051
Schneider, Gregory F; Shaw, Bryan F; Lee, Andrew et al. (2008) Pathway for unfolding of ubiquitin in sodium dodecyl sulfate, studied by capillary electrophoresis. J Am Chem Soc 130:17384-93

Showing the most recent 10 out of 38 publications