Neville Kallenbach's Research Interests

One of the most rapidly advancing areas of modern chemistry lies at the interface between chemistry and biology. Modern biology and genetics constantly raise important and fundamental questions that need to be addressed by physical chemical methods. Some of these questions of interest to my group include: How do proteins fold into their native three-dimensional structures, which are biologically active? How do proteins fold in membrane environments? Can proteins be engineered to create novel materials? How do proteins read DNA structure, when binding is determined by structural signals and not by sequence?

kallenbach_illu.jpgMy group brings a combination of spectroscopy, foot-printing techniques, thermody-namic analysis, and NMR structure determination to bear on the above questions, using a series of simple model systems that are synthesized chemically or biochemically by cloning and expression of proteins such as myoglobin and high-mobility group DNA binding pro-teins. The long-term objective is to design new peptides and proteins with specified functions, including agents that can intervene in important cellular processes, such as viral integration, and DNA repair or recombination.

Recent research from this laboratory has led to the following results:

  • Determination of the intrinsic free energy of alpha helix stabilization by alanine, leucine, glycine, using a new method based on measuring isotope exchange rates of the peptide group in short helical fragments of proteins.
  • A new method for mapping the surface of proteins and areas of interaction between proteins, based on cleavage of labeled proteins with enzymes or use of synch-rotron radiation.
  • Demonstration of branched inter-mediates in the pairing of DNA chains containing repetitive sequences. Requirements for DNA binding by HMG proteins, a family of nuclear proteins that are involved in DNA compaction and transcriptional control.
  • Determination of structural signals for capping the ends of alpha helices in peptides and proteins by H-bonds and van der Waals interactions between side chains and the peptide backbone.
  • Definition of the unfolded state of proteins using isotope-edited NMR experiments.
Updated on 09/07/2005