(745e) Self-Assembly and DNA Binding Properties of Bzip Peptide Amphiphiles

GCN4 is a well-characterized protein in yeast that is a member of the AP-1 family of transcription factors. This work involves a thirty eight amino acid ?bZip? peptide derived from GCN4 that contains a leucine zipper based dimerization segment and a basic DNA binding region. Conjugating bZip to a hydrophobic carbon chain tail promotes the formation of cylindrical micelles in aqueous solution. Circular dichroism has shown that the peptides adopt a higher degree of alpha-helical secondary structure in the micelle corona compared to the unaggregated monomers. Enhanced secondary structure facilitates the DNA binding of bZip peptide amphiphiles in a fashion similar to the native protein, in contrast to the unmodified peptide. The specificity of the DNA binding to the AP-1 target site versus other sequences is currently under examination. Modification of the peptide amphiphiles to drive assembly into different shaped aggregates is also being studied.

Biofunctional bZip constructs may have applications as artificial transcription factors or gene delivery vehicles. Future work will include in vitro cell assays of bZip peptide amphiphile micelles to determine their biological potential. The micelles could be engineered to incorporate peptides with other functionalities such as cellular uptake and nuclear targeting.