Forum 10/23/2003

“Affinity-directed linkage of oligo-DNA to an enzyme: technology to enable functional, self-assembling protein arrays”

Gavin Meredith – Physiology & Biophysics, UC Irvine

I have synthesized a novel photo-activatable compound that can be used to create a covalent link between single strands of DNA and histidine-tagged recombinant protein molecules.  The resultant hybrid molecules are one-to-one compounds of protein and DNA.  The approach is general and should be applicable to a large number of proteins.  When the target protein is an enzyme, it is critical to be able to direct the attachment of the DNA to minimize interference with its catalytic function.  This strategy provides for rational design since the linkage can be targeted to a specific region on the surface of the target protein (the position of the his-tag), well away from the active site or other important surfaces. In the absence of knowledge of the protein’s structure, a combinatorial approach could be taken to obtain useful hybrid molecules.  Ultimately, this approach could also be parallelized to yield a multitude of hybrid molecules, each type bearing a unique DNA sequence.  One pending application of this technology is to convert a DNA array into a spontaneously self-assembled functional protein array.