Can the Ph.D. libraries be used to find the natural ligands for a given protein?
Since the Ph.D. libraries consist of fully randomized peptides displayed on phage, a binding peptide identified in a particular panning experiment will not necessarily correspond to a “natural” ligand for the target. The biopanning procedure iteratively selects for those peptides which best bind the target under the panning conditions in vitro, without regard to the biological role of the target in vivo. For certain targets, such as antibodies with linear epitopes, the selected sequence will in all likelihood correspond to that region of your antigen recognized by the antibody. For targets which bind to large surfaces of a protein, or discontinuous regions of the primary sequence, the selected sequences are less likely to resemble the “natural” ligand. As a result, caution should be taken if you are planning on using the DNA corresponding to the selected sequences as probes when trying to clone any natural ligand proteins. In contrast, cDNA expression libraries are by nature limited to
