In vitro selection from molecular libraries has rapidly come of age as
a protein-engineering tool. Dramatic increases in protein affinity ca
n be engineered using phage-display libraries, and specific antibodies
can be selected directly from a single 'naive' library of their genes
. Repertoires of small molecules are a potentially valuable resource f
or drug discovery. Libraries of linear peptides provide ligands for pr
oteins that recognize continuous epitopes, and low-affinity mimics of
some small molecules, but generally do not contain mimics of large mol
ecular interfaces. Switching to constrained peptide formats, and deplo
ying more diverse, non-peptide chemical libraries, may bring greater s
uccess.