Formation of dimers via leucine zippers is an absolute requirement for several transcription factors to express their activity. Using circular dichroism spectroscopy, it was found that synthetic peptides which mimic the leucine zippers from CREB, Jun and Myc are alpha-helices in solution. The CREB leucine zipper peptide specifically inhibited the binding of wild type CREB protein and transcription from the CRE containing c-fos promoter in vitro. This inhibition is most likely caused by competition of the peptide to form complex with CREB monomers through leucine zippers.