Combinatorial Peptide Libraries: Mining for Cell-Binding Peptides

Methods of selecting cell-targeting ligands from peptide libraries and the use of these peptides were studied. While phage display methods have been the predominant library type used, other peptide library formats have also been used to isolate cell-targeting agents. Cell targeting peptides can have affinities comparable to those of clinically used antibodies and represent a new tool for directing targeting therapies and imaging agents. It is important to remember that the isolated ligands are rarely the optimal peptide sequence and should be considered lead compounds, yet by blending biology and chemistry, peptide leads can be optimized for affinity, specificity, activity, stability, solubility, and biodistribution. AMG-386 (trebananib), is in phase III clinical trials for treatment of a variety of cancer types. The peptide prevents binding of angiopoietin-1 and angiopoietin-2 to Tie2. The fat-targeting peptide CKGGRAKDC linked to the D-enantiomer of the proapoptotic (KLAKLAK)2 peptide entered phase I trial in early 2012 under the name Adipotide.