Drug Discovery for Breast Cancer by Mirror-Image Display

摘要

Two limitations inherent in phage display are the relatively small library size (less than 10(9)) and the constraint that the building blocks of the library be restricted to the 20 naturally-occurring amino acids. These constraints likely prevented us from identifying ligands for the MUC-l target form two different phage display libraries, and we have therefore been compelled to seek an alternative method for the presentation of larger and more diverse libraries of potential ligands to the MUC-l target. The purified translation system we have developed has the potential to overcome both restrictions. encumbering phage display because of a much larger library size and an expanded range of unnatural amino acid building blocks beyond the 20 naturally-occurring amino acids. We have now demonstrated that our purified translation system is capable of synthesizing peptidomimetics with unnatural amino acids encoded at sequential positions of the oligomer. A library of such peptidomimietics should overcome the inherent limitations of mirror image display that requires chemically synthesized small targes.