Peptide aptamers have emerged as powerful new tools for molecular medicine. They 
can specifically bind to and functionally inactivate a given target molecule 
under intracellular conditions. Typically, peptide aptamers are generated by 
screening a randomized peptide expression library, displayed from the 
Escherichia coli thioredoxin A (TrxA) protein. Here, we transferred peptide 
moieties from defined TrxA-based peptide aptamers to alternative scaffold 
proteins, such as the green fluorescent protein and staphylococcal nuclease. 
Yeast and mammalian two-hybrid assays as well as in vitro binding analyses show 
that the TrxA scaffold can be a major determinant for the binding of peptide 
aptamers. In addition, we demonstrate that TrxA can correctly display peptide 
sequences that correspond to the binding domains of natural interaction 
partners. Therefore, sequence analyses of TrxA-based peptide aptamers, isolated 
by two-hybrid screening from randomized expression libraries, should also be 
useful to find cellular binding partners for a given target protein, by 
homology.