A SYNTHETIC PEPTIDE LIGASE

The preparation of synthetic molecules showing the remarkable efficien cies characteristic of natural biopolymer catalysts remains a formidab le challenge for chemical biology, Although significant advances have been made in the understanding of protein structure and function, the ne novo construction of such systems remains elusive(1-5). Re-engineer ed natural enzymes and catalytic antibodies, possessing tailored bindi ng pockets with appropriately positioned functional groups, have been successful in catalysing a number of chemical transformations, sometim es with impressive efficiencies(6-11). But efforts to produce wholly s ynthetic catalytic peptides have typically resulted in compounds with questionable structural stability, let alone reactivity(1). Here we de scribe a 33-residue synthetic peptide, based on the coiled-coil struct ural motif(12-14), which efficiently catalyses the condensation of two shorter peptide fragments with high sequence-and diastereoselectivity . Depending on the substrates used, we observe rate enhancements of te nfold to 4,100-fold over the background, with catalytic efficiencies i n excess of 10(4). These results augur well for the rational design of functional peptides.