Inhibition of pancreatic cancer cell growth by designed peptides

BIOL 125

Jeffrey Hartgerink1, Lorenzo Aulisa, aulisa@rice.edu1, Nico Foraz2, and Colin McGuckin3. (1) Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, (2) Dept. of Regenerative Medicine, Univ. of Newcastle upon Tyne, (3) Department of Regenerative Medacine, Univ. of Newcastle upon Tyne
HOX proteins bind to the DNA through a highly conserved 60 amino acid sequence (the homeodomain) and greater DNA-binding specificity and stability are achieved when it forms heterodimers with the co-factor PBX. In different oncogenic transformations, deregulated HOX gene expression has been observed, indicating an involvement of these transcriptional regulators in carcinogenesis and metastasis. Inhibition of HOX-PBX interaction could be a good strategy to control the abnormal proliferation of the cancer cells. A small peptide derivative was designed which shows good inhibition of the growth of T3M4 pancreatic cancer cells. This molecule contains three critical regions for the reduction of cancer cell proliferation: a 9 amino acid sequence designed to disrupt HOX/PBX/DNA complex formation, a 16 amino acid sequence to deliver the peptide into the cell and a 16 carbon acyl chain which significantly enhances the potency of the combined 25 amino acid peptide component.
 

Chemistry and Metabolism
4:30 PM-6:30 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster

Division of Biological Chemistry

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