In this project we will exploit a bionanotechnology developed at City of Hope to link multiple copies of a growth factor activator peptide (e.g. Heregulin, Epidermal Growth Factor) to two or three-armed DNA struts. The system is self-assembling and takes advantage of the capacity of bacterial methyltransferases to serve as targeting devices that can covalently link fusion proteins to precise sites on DNA. The device thus formed is expected to inhibit HERS or EGFR kinase activation by blocking one or more of structural transitions leading to dimerization or oligomerization of the receptor. The devices display the growth factor ligand in a two dimensional array suitable for capture of multiple extracellular domains of the receptor. Moreover, they can be tracked by appropriately labeling the DNA and have the advantage of increased binding affinity due to the multivalent display of growth factors. Our preliminary results show that a device displaying multiple copies of the growth factor ligand heregulin can bind to cancer cells.
| Smith, Steven S (2006) Nucleoprotein assemblies at the nanoscale: medical implications. Nanomedicine (Lond) 1:427-36 |
| Singer, Elizabeth M; Smith, Steven S (2006) Nucleoprotein assemblies for cellular biomarker detection. Nano Lett 6:1184-9 |
