(19)F-encoded combinatorial libraries: discovery of selective metal binding and catalytic peptoids.
A (19)F NMR method for encoding of combinatorial libraries has been developed. Aryl fluorides whose chemical shifts are modified by aromatic substituents were prepared and attached to resin support beads that were used in the split-pool synthesis of peptoids. The detection of the (19)F NMR signal of tags derived from a single "big bead" was demonstrated. The library diversity arises from peptoid amines and the cyclic anhydrides used in their acylation. The resulting 90-compound library was examined for metal ion binding, and novel ligands for iron and copper were discovered. Their binding constants were determined to be in the low micromolar range using conventional methods. The library was also examined for autocatalysis of acylation, and a molecule possessing the catalytic triad of serine proteases was deduced.
Pirrung
Michael C
MC
Department of Chemistry, Levine Science Research Center, Box 90317, Duke University, Durham, North Carolina 27708-0317, USA.
Park
Kaapjoo
K
Tumey
L Nathan
LN
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008670:Metals / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D034444:Peptoids; D011485:Protein Binding; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D008670:Metals; D010455:Peptides; D034444:Peptoids; D005461:Fluorine